☆ 4.7 Review

The molecular basis for cellular function of intrinsically disordered protein regions

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A context-dependent and disordered ubiquitin-binding motif

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Disordered Regions Flanking the Binding Interface Modulate Affinity between CBP and NCOA

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Transcription factors perform a 2-step search of the nucleus

Max Valentin Staller

Summary: Transcription factors regulate gene expression by binding to DNA and recruiting protein complexes. This process can be divided into two steps, DNA-binding and protein-binding, to locate appropriate binding sites in the eukaryotic genome.

GENETICS (2022)

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Article Biochemistry & Molecular Biology

WNK kinases sense molecular crowding and rescue cell volume via phase separation

Cary R. Boyd-Shiwarski et al.

Summary: When cells are exposed to hypertonicity, WNK kinases form condensates to activate ion influx, thereby restoring cell volume and ensuring cell survival.

CELL (2022)

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Article Cell Biology

Evolution of short linear motifs and disordered proteins Topic: yeast as model system to study evolution

Ami G. Sangster et al.

Summary: Evolutionary preservation of protein structure has made a significant impact on the field of molecular evolution. In the last decade, major progress has been made in understanding the evolution of intrinsically disordered regions (IDRs), facilitated by new experimental and computational approaches in yeast.

CURRENT OPINION IN GENETICS & DEVELOPMENT (2022)

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Article Biochemistry & Molecular Biology

Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding

Dajun Sang et al.

Summary: Phase separation can concentrate biomolecules and accelerate reactions. By engineering phosphorylation reactions within synthetic condensates, this study found that phosphorylation dynamics are rapid within condensates and can drive cell localization changes. High client concentration and the availability of many excess client-binding sites are crucial for efficient phosphorylation within condensates, and macromolecular crowding also modulates phosphorylation. This study provides important insights into cellular signaling mechanisms.

MOLECULAR CELL (2022)

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Article Multidisciplinary Sciences

Structures of α-synuclein filaments from human brains with Lewy pathology

Yang Yang et al.

Summary: Parkinson's disease (PD) is a common movement disorder characterized by resting tremor, rigidity, bradykinesia and postural instability. It is associated with the presence of alpha-synuclein inclusions in brain cells. Many PD patients develop dementia after several years of diagnosis. PD dementia (PDD) is similar to dementia with Lewy bodies (DLB), which is diagnosed when cognitive impairment precedes parkinsonian motor signs or begins within one year from their onset.

NATURE (2022)

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Article Multidisciplinary Sciences

Connecting sequence features within the disordered C-terminal linker of Bacillus subtilis FtsZ to functions and bacterial cell division

Min Kyung Shinn et al.

Summary: Intrinsically disordered regions (IDRs) play a role in autoregulating folded enzymes. The C-terminal tail (CTT) of bacterial cell division protein FtsZ, which includes a disordered C-terminal linker (CTL) and a well-conserved C-terminal peptide (CT17), has been found to make contacts with the T7 loop. Nonrandom sequence patterns within the CTL mediate CTT-core interactions and modulate FtsZ functionalities.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Biochemistry & Molecular Biology

Intrinsic protein disorder uncouples affinity from binding specificity

Tamas Lazar et al.

Summary: It has been assumed that the major advantage of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) is the decoupling of specificity from binding strength. However, limited experimental evidence has been found to support this assumption. Through the analysis of a dataset of well-characterized ID/globular protein complexes, it has been revealed that the affinity distributions of IDP/globular and globular/globular complexes show different trends, suggesting that specificity does not necessarily indicate weaker binding strength for IDPs/IDRs.

PROTEIN SCIENCE (2022)

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Article Multidisciplinary Sciences

Small molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states

Jiaqi Zhu et al.

Summary: This study elucidates the atomically detailed binding mechanisms of small molecule drugs to the intrinsically disordered region of the androgen receptor, providing insights for developing more potent inhibitors and strategies for disordered protein drug design.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems

Keren Lasker et al.

Summary: Intracellular phase separation is a universal principle for organizing biochemical reactions. The material properties of condensates formed by the protein PopZ in Caulobacter crescentus are determined by a balance between attractive and repulsive forces. Disrupting this balance results in condensates with different material properties. Condensates with specific material properties are important for proper cell division and organismal fitness.

NATURE COMMUNICATIONS (2022)

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Article Cell Biology

Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease

Brandon J. Payliss et al.

Summary: The study shows that CDK1-cyclin B phosphorylates specific residues of SLX4 in the MUS81-binding region, leading to relaxation of substrate specificity of MUS81-EME1 and stimulation of cleavage of replication and recombination structures. Phosphorylation also promotes high-affinity interaction between SLX4 and MUS81, driving recruitment and activation of MUS81-EME1.

CELL REPORTS (2022)

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Article Biochemistry & Molecular Biology

Intrinsic protein disorder uncouples affinity from binding specificity

Tamas Lazar et al.

Summary: This article explores the relationship between intrinsic disorder in proteins and the specificity and affinity of their binding with globular proteins. By analyzing the structures and free energy of complexes, the authors found that the specificity of IDPs/IDRs does not necessarily correlate with weaker binding strength.

PROTEIN SCIENCE (2022)

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Review Chemistry, Multidisciplinary

NMR Provides Unique Insight into the Functional Dynamics and Interactions of Intrinsically Disordered Proteins

Aldo R. Camacho-Zarco et al.

Summary: Intrinsically disordered proteins play essential roles in cellular and extracellular biochemistry. Nuclear magnetic resonance is a powerful tool for studying their structural and dynamic behavior, providing insights into reaction kinetics and thermodynamics essential for function. Recent applications of NMR have helped uncover the mechanistic basis of functional disordered molecular assemblies important for human health.

CHEMICAL REVIEWS (2022)

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Article Biochemistry & Molecular Biology

Disorder in a two-domain neuronal Ca2+-binding protein regulates domain stability and dynamics using ligand mimicry

Lasse Staby et al.

Summary: The presence of intrinsically disordered proteins (IDPs) has complicated the understanding of the relationship between sequence, structure, and function of proteins. This study demonstrates that the loss of a disordered tail in a calcium-sensing protein significantly affects stability, dynamics, and folding behavior of ordered domains, indicating a close relationship between order and disorder in protein properties. The findings suggest potential implications for designing investigations into mixed systems and targeting drug development based on this behavior.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Clustering of Aromatic Residues in Prion-like Domains Can Tune the Formation, State, and Organization of Biomolecular Condensates

Alex S. Holehouse et al.

Summary: The research reveals that Velol protein forms solid-like assemblies in Balbiani bodies, and manipulating its structure or design can alter its internal dynamics, offering insights for the design of synthetic condensates.

BIOCHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

The flexible N-terminus of BchL autoinhibits activity through interaction with its [4Fe-4S] cluster and released upon ATP binding

Elliot Corless et al.

Summary: In bacteriochlorophyll biosynthesis, the reduction of protochlorophyllide to chlorophyllide is catalyzed by dark-operative protochlorophyllide oxidoreductase. This process is regulated by ATP-induced conformational changes, and the flexible N-terminal region plays a role in autoinhibition. The release of this region upon ATP binding leads to specific conformational changes, promoting complex formation and protochlorophyllide reduction.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

Order through disorder: The role of intrinsically disordered regions in transcription factor binding specificity

Sagie Brodsky et al.

Summary: Transcription factors (TFs) recognize specific DNA sequences through DNA-binding domains (DBDs), but the presence of intrinsically disordered regions (IDRs) also play a crucial role in DNA binding specificity.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2021)

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Article Cell Biology

Adaptable P body physical states differentially regulate bicoid mRNA storage during early Drosophila development

M. Sankaranarayanan et al.

Summary: Ribonucleoprotein condensates can exhibit diverse physical states, with specific proteins, protein-protein interactions, and RNA regulating their properties. In this study, the physical properties of processing bodies (P bodies) in mature Drosophila oocytes were investigated, showing how the arrested state of P bodies supports mRNA storage and how egg activation modulates P body properties to release mRNA for translation in the early embryo. This work provides insight into how the physical states of condensates regulate cellular function in development.

DEVELOPMENTAL CELL (2021)

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Article Biochemistry & Molecular Biology

Flanking Disorder of the Folded αα-Hub Domain from Radical Induced Cell Death1 Affects Transcription Factor Binding by Ensemble Redistribution

Lasse Staby et al.

Summary: Protein intrinsic disorder plays a crucial role in the organization of transcription regulatory interactomes. The study shows how flanking disorder can influence the conformation and binding affinity of folded proteins, suggesting an adaptation to various transcription factor ligands. This research highlights the importance of disordered regions in tuning the fold and function of modular proteins.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Chemistry, Multidisciplinary

Quantitative Description of Intrinsically Disordered Proteins Using Single-Molecule FRET, NMR, and SAXS

Samuel Naudi-Fabra et al.

Summary: Studying the conformational landscape of intrinsically disordered and partially folded proteins is challenging and requires an integrated approach using multiple techniques to accurately describe the conformational ensembles of these proteins. This integrated approach has been successfully tested and validated, providing new insights into the conformational landscape of viral proteins and demonstrating its potential for integrative dynamic structural biology.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Multidisciplinary Sciences

Cold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression

Pan Zhu et al.

Summary: Plants use seasonal temperature cues to regulate flowering time, with cold conditions affecting transcription of FLC to achieve vernalization. Cold rapidly increases the formation of FRI nuclear condensates that do not colocalize with active FLC loci, while warm temperatures reverse this process to buffer FLC shutdown.

NATURE (2021)

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Article Multidisciplinary Sciences

Structure-based classification of tauopathies

Yang Shi et al.

Summary: The structures of tau filaments from different tauopathies vary, allowing for a hierarchical classification of these diseases. Some tauopathies share similar filament folds, while others have distinct folding patterns.

NATURE (2021)

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Article Chemistry, Multidisciplinary

A short peptide synthon for liquid-liquid phase separation

Manzar Abbas et al.

Summary: Liquid-liquid phase separation is crucial in creating cellular compartments and protocells, and the design of short peptide synthons for phase separation is significant. These synthons can concentrate biomolecules and catalyze anabolic reactions, showing potential for new coacervate-based protocells.

NATURE CHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

Molecular interactions contributing to FUS SYGQ LC-RGG phase separation and co-partitioning with RNA polymerase II heptads

Anastasia C. Murthy et al.

Summary: FUS mediates phase separation in biomolecular condensates with the help of RGG domains and interacts with RNA polymerase II through various residue types and interaction modes. NMR visualization reveals a wider array of residue types and interaction modes stabilizing the phase-separated FUS and RNA polymerase II domains in transcriptional condensates.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2021)

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Article Multidisciplinary Sciences

Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling

Louis-Philippe Bergeron-Sandoval et al.

Summary: Endocytic coat proteins with prion-like domains form hemispherical puncta in budding yeast, which act as biomolecular condensates to organize proteins at the membrane for actin-dependent endocytosis. These endocytic condensates are reversible, forming and dissolving in response to temperature and solution conditions, and are organized around dynamic protein-protein interaction networks.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Multidisciplinary Sciences

Accurate model of liquid-liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties

Giulio Tesei et al.

Summary: Researchers have found that many intrinsically disordered proteins (IDPs) can participate in the formation of membraneless organelles in the cell. Investigating the phase behavior of IDPs through molecular simulations requires an accurate description of intramolecular and intermolecular interactions. By developing a coarse-grained model based on experimental data, the model accurately reproduces the conformational propensities of IDPs.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biochemistry & Molecular Biology

Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation

Erik W. Martin et al.

Summary: The study demonstrates that the interaction between folded and disordered domains can modulate the phase separation behavior of the RNA-binding protein hnRNPA1, even in the absence of RNA. The presence of folded domains can alter the salt dependence of phase separation, and the mechanism of interaction with the LCD provides an explanation for the observed salt-dependent phase separation.

NUCLEIC ACIDS RESEARCH (2021)

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Article Multidisciplinary Sciences

A ubiquitous disordered protein interaction module orchestrates transcription elongation

Katerina Cermakova et al.

Summary: A common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs) is identified during eukaryotic transcription elongation, which plays a critical role in gene expression and RNAP2 elongation dynamics.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Ligand effects on phase separation of multivalent macromolecules

Kiersten M. Ruff et al.

Summary: Biomolecular condensates concentrate biomolecules into non-stoichiometric assemblies, enabling spatial and temporal control over cellular processes. Ligands can modulate the phase behavior of scaffolds, affecting the formation and dissolution of condensates. Different types of ligands have varying effects on the stability of condensates, with monovalent ligands destabilizing condensates and multivalent ligands either stabilizing or destabilizing them.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biology

Identifying molecular features that are associated with biological function of intrinsically disordered protein regions

Taraneh Zarin et al.

Summary: This study aims to utilize molecular features within the intrinsically disordered regions (IDRs) of proteins to predict specific biological functions and identify associated features. The results show diverse predictable functions, with some features consistent with previous reports and others previously unknown. Feature analysis represents a new systematic approach to understanding how biological functions of IDRs are determined by their protein sequences.

ELIFE (2021)

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Article Biochemistry & Molecular Biology

Hyperphosphorylation of Human Osteopontin and Its Impact on Structural Dynamics and Molecular Recognition

Borja Mateos et al.

Summary: Protein phosphorylation is a key regulator of protein functionality, especially for intrinsically disordered proteins. Changes in the molecular environment, particularly through phosphorylation, can modulate the structural features of proteins. The study highlights the importance of electrostatic and hydrophobic interactions in forming compact substates in IDPs and their relevance for molecular recognition events.

BIOCHEMISTRY (2021)

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Article Biology

A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers

Theresa Hwang et al.

Summary: The study reveals that the protein PCARE has a high specificity for binding to ENAH over paralogs VASP and EVL, inhibiting ENAH-dependent adhesion in cells. PCARE achieves specificity by stabilizing a conformation of the ENAH EVH1 domain that is inaccessible to other family members. The research uncovers a mechanism of interaction specificity that can differentiate highly similar paralogs and provides tools for studying Ena/VASP functions in processes such as cancer cell invasion.

ELIFE (2021)

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Article Biophysics

Intrachain interaction topology can identify functionally similar intrinsically disordered proteins

Jonathan Huihui et al.

Summary: Functionally similar IDPs often lack sequence similarity, posing a challenge for traditional sequence alignment-based functional classification. Recent advances in heteropolymer theory have introduced a powerful set of sequence-patterning metrics that can identify functionally similar IDPs, providing an alternate approach for functional classification.

BIOPHYSICAL JOURNAL (2021)

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Article Biochemistry & Molecular Biology

Physics-based computational and theoretical approaches to intrinsically disordered proteins

Joan-Emma Shea et al.

Summary: Intrinsically disordered proteins (IDPs) are a special class of proteins that do not fold into specific 3D shapes, making experimental studies challenging and requiring theoretical and computational methods. Recent progress has been made in developing new computational and theoretical approaches to study the structure and dynamics of IDPs, particularly their phase separation into protein-rich condensates.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2021)

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Article Biochemical Research Methods

Critical assessment of protein intrinsic disorder prediction

Marco Necci et al.

Summary: Intrinsically disordered proteins present a challenge to traditional protein structure-function analysis, with computational methods, particularly deep learning techniques, showing superior performance in predicting disorder. However, predicting disordered binding regions remains difficult, and there is a significant variation in computational times among methods.

NATURE METHODS (2021)

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Article Multidisciplinary Sciences

Nucleosome plasticity is a critical element of chromatin liquid-liquid phase separation and multivalent nucleosome interactions

Stephen E. Farr et al.

Summary: The authors develop a multi-scale chromatin model to investigate the effects of DNA breathing on nucleosome valency, heterogeneity, and dynamics, promoting disordered folding and LLPS.

NATURE COMMUNICATIONS (2021)

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Article Biochemical Research Methods

How multisite phosphorylation impacts the conformations of intrinsically disordered proteins

Fan Jin et al.

Summary: The study found that multi-site phosphorylation causes V-shaped changes in collapse propensity of all proteins based on their initial net charge, expanding neutral or overall negatively charged IDPs and shrinking positively charged IDPs. In two of the IDPs, only two biologically relevant phosphorylation sites are enough to significantly expose the adjacent negatively charged active site, increasing the likelihood of interaction with other binding partners.

PLOS COMPUTATIONAL BIOLOGY (2021)

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Article Biology

Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator

Adrian L. Sanborn et al.

Summary: 150 ADs were identified, with most (73%) binding to the Med15 subunit of Mediator, and binding strength correlated with activation. AD-Mediator interaction is a dynamic 'fuzzy' binding process without shape complementarity. Mutagenesis revealed biochemical and structural constraints, and a neural network accurately predicted ADs in human proteins and other yeast proteins.

ELIFE (2021)

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Article Multidisciplinary Sciences

DEAD-box helicases modulate dicing body formation in Arabidopsis

Qi Li et al.

Summary: The RNA helicases RH6, RH8, and RH12 play key roles in modulating the formation of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis via liquid-liquid phase separations (LLPSs). Their accumulation decreases in the nuclei upon Turnip mosaic virus infections, leading to a decrease in D-bodies.

SCIENCE ADVANCES (2021)

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Review Biochemistry & Molecular Biology

On the specificity of protein-protein interactions in the context of disorder

Kaare Teilum et al.

Summary: Intrinsically disordered proteins (IDPs) share similar specificity with globular proteins quantitatively, but have larger interactome sizes, adaptability, and a higher degree of multivalency. This allows for new interaction mechanisms and challenges traditional concepts of specificity.

BIOCHEMICAL JOURNAL (2021)

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Article Biophysics

Metapredict: a fast, accurate, and easy-to-use predictor of consensus disorder and structure

Ryan J. Emenecker et al.

Summary: Consensus disorder scores integrate multiple independent predictors to provide a per-residue value reflecting the number of tools predicting disorder.

BIOPHYSICAL JOURNAL (2021)

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Article Biochemistry & Molecular Biology

A prion-like protein regulator of seed germination undergoes hydration-dependent phase separation

Yanniv Dorone et al.

Summary: The study identified a protein named FLOE1 that helps plant seeds sense water stress and regulate germination under unfavorable conditions. It was demonstrated that the biophysical states of the protein can modulate its function, while different types of variations of this protein exist in natural populations and are associated with adaptive germination strategies in plants.

CELL (2021)

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Review Biochemistry & Molecular Biology

AlphaFold and Implications for Intrinsically Disordered Proteins

Kiersten M. Ruff et al.

Summary: Accurate predictions of protein structures using AlphaFold have made significant progress. Most protein sequences in the human proteome have been structurally annotated, with over 30% of regions being disordered.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Multidisciplinary Sciences

Highly accurate protein structure prediction with AlphaFold

John Jumper et al.

Summary: Proteins are essential for life, and accurate prediction of their structures is a crucial research problem. Current experimental methods are time-consuming, highlighting the need for accurate computational approaches to address the gap in structural coverage. Despite recent progress, existing methods fall short of atomic accuracy in protein structure prediction.

NATURE (2021)

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Article Multidisciplinary Sciences

Highly accurate protein structure prediction for the human proteome

Kathryn Tunyasuvunakool et al.

Summary: Using the AlphaFold method, the structural coverage of the proteome has been significantly expanded, covering 98.5% of human proteins with 58% of residues having confident predictions and 36% having very high confidence. Introducing new metrics to interpret the dataset and identify disordered regions, this study aims to provide high-quality predictions for generating biological hypotheses.

NATURE (2021)

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Article Biochemistry & Molecular Biology

Mechanistic dissection of increased enzymatic rate in a phase-separated compartment

William Peeples et al.

Summary: Biomolecular condensates concentrate macromolecules into discrete cellular foci without an encapsulating membrane, leading to accelerated reaction rates through increased concentrations and physical organization of molecules. The SUMOylation enzyme cascade can be recruited into droplets generated by liquid-liquid phase separation, significantly increasing reaction rates with substantial specificity among different substrates. This modulation of reaction rates in condensates is achieved through mass action and changes in substrate K-M, likely due to scaffold-induced molecular organization.

NATURE CHEMICAL BIOLOGY (2021)

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Article Multidisciplinary Sciences

The sequence-ensemble relationship in fuzzy protein complexes

San Hadzi et al.

Summary: The structural characteristics of IDPs bound to their targets are determined by a combination of IDP sequence and the distribution of IDP-target interaction hotspots, explaining the observed structural heterogeneity of fuzzy complexes. The presented model successfully reproduces the dynamical signatures of target-bound IDPs from NMR relaxation experiments and the changes in interaction affinity and IDP helicity induced by mutations. The model elucidates how the target-bound IDP ensemble adapts to mutations to achieve an optimal balance between conformational freedom and interaction energy.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biochemistry & Molecular Biology

Previously uncharacterized interactions between the folded and intrinsically disordered domains impart asymmetric effects on UBQLN2 phase separation

Tongyin Zheng et al.

Summary: The shuttle protein UBQLN2 functions in protein quality control by binding to proteasomal receptors and ubiquitinated substrates through its UBL and UBA domains, respectively. The interplay between the folded domains and intrinsically disordered regions mediates liquid-liquid phase separation of UBQLN2. The interactions between UBL and UBA domains, as well as disordered regions, are crucial for understanding the phase behavior and physiological functions of UBQLN2.

PROTEIN SCIENCE (2021)

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Article Multidisciplinary Sciences

Accurate prediction of protein structures and interactions using a three-track neural network

Minkyung Baek et al.

Summary: Through the three-track network, we achieved accuracies approaching those of DeepMind in CASP14, enabling rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and providing insights into the functions of proteins with currently unknown structure.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics

C. J. Markin et al.

Summary: A high-throughput microfluidic enzyme kinetics platform, HT-MEK, was studied for simultaneous expression, purification, and characterization of over 1500 enzyme variants. Through more than 670,000 reactions on 1036 mutants of alkaline phosphatase PafA, over 5000 kinetic and physical constants were determined, uncovering underlying enzyme architecture.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells

Cesar L. Cuevas-Velazquez et al.

Summary: This study introduces a new FRET biosensor, SED1, developed using Arabidopsis intrinsically disordered AtLEA4-5 protein to monitor osmotic stress induced changes in cells. The biosensor demonstrates high sensitivity to osmolarity changes and shows near-linear responses in various living cells, offering a valuable tool for studying water-associated stress. The research highlights the potential of intrinsically disordered protein regions as environmentally-responsive molecular tools across different organisms.

NATURE COMMUNICATIONS (2021)

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Article Genetics & Heredity

A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling

Ian S. Hsu et al.

Summary: The study focused on the intrinsically disordered regions (IDRs) controlling the stochastic pulsing dynamics of the transcription factor Crz1 in fungi. They found that while Crz1 IDRs from anciently diverged fungi transiently respond to calcium stress, only those from the Saccharomyces clade support pulsatility, encode extra information, and enhance fitness in competition assays. Additionally, they observed the conservation of Crz1 pulsing in distantly related fungi, suggesting stabilizing selection on the signaling phenotype. The authors propose that the evolutionary flexibility of functionally divergent IDRs underlies the conservation of stochastic signaling by stabilizing selection.

PLOS GENETICS (2021)

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Article Microbiology

Entropy-driven translocation of disordered proteins through the Gram-positive bacterial cell wall

David K. Halladin et al.

Summary: Entropy plays a crucial role in translocating disordered transmembrane proteins through the Gram-positive cell wall, as shown by experimental validation. The study demonstrates that entropic forces are sufficient to drive the translocation of specific proteins to the outer surface.

NATURE MICROBIOLOGY (2021)

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Article Multidisciplinary Sciences

Order and disorder-An integrative structure of the full-length human growth hormone receptor

Noah Kassem et al.

Summary: This study uses methods such as small-angle X-ray scattering to investigate the structure of the human growth hormone receptor, revealing a broad structural ensemble in hGHR that emphasizes the need to view signaling in disease states from an ensemble perspective. This is the first experimental model of any full-length cytokine receptor in a lipid membrane.

SCIENCE ADVANCES (2021)

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Article Biochemistry & Molecular Biology

Folded domain charge properties influence the conformational behavior of disordered tails

Ishan Taneja et al.

Summary: The relative position and accessibility of charged residues across the surface of a folded domain can dictate IDR conformational behavior, overriding expectations based on net surface charge properties. Naturally occurring proteins possess multiple charge patches that are physically accessible to local IDRs. Even modest changes in the local electrostatic environment of a folded domain can substantially modulate IDR-folded domain interactions.

CURRENT RESEARCH IN STRUCTURAL BIOLOGY (2021)

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Article Computer Science, Interdisciplinary Applications

Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy

Jerelle A. Joseph et al.

Summary: Mpipi is a multiscale coarse-grained protein model that quantitatively describes the change in protein critical temperatures with respect to amino acid sequence, considering the dominant role of pi-pi and hybrid cation-pi/pi-pi interactions, and the stronger attractive contacts of arginines compared to lysines. Experimental benchmarks demonstrate that Mpipi predictions are in good agreement with experimental results, and the model can accurately predict protein-RNA interactions and liquid-liquid phase separation trends of proteins with sequence mutations.

NATURE COMPUTATIONAL SCIENCE (2021)

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Article Biochemistry & Molecular Biology

PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins

Tamas Lazar et al.

Summary: The Protein Ensemble Database (PED) has been significantly updated to version 4.0, with cutting-edge technology and an increased amount of data. The database now includes a renewed graphical interface, interactive feature viewer, and high-quality data guaranteed by a new submission process. Additionally, a new search engine allows users to build advanced queries and search all entry fields.

NUCLEIC ACIDS RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Pfam: The protein families database in 2021

Jaina Mistry et al.

Summary: The Pfam database has recently added a large number of protein families and domains, made revisions for COVID-19 research, and introduced Pfam-B as a supplement. These updates and improvements can help researchers classify protein sequences more effectively and conduct related studies.

NUCLEIC ACIDS RESEARCH (2021)

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Article Biochemistry & Molecular Biology

IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions-Insights from transcription factors

Peter S. Millard et al.

PROTEIN SCIENCE (2020)

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Article Biophysics

Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions

Jeong-Mo Choi et al.

Annual Review of Biophysics (2020)

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Review Biochemistry & Molecular Biology

Emerging consensus on the collapse of unfolded and intrinsically disordered proteins in water

Robert B. Best

CURRENT OPINION IN STRUCTURAL BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

Binding without folding - the biomolecular function of disordered polyelectrolyte complexes

Benjamin Schuler et al.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2020)

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Article Chemistry, Physical

Development of a Force Field for the Simulation of Single-Chain Proteins and Protein-Protein Complexes

Stefano Piana et al.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2020)

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Review Biochemistry & Molecular Biology

Water as a Good Solvent for Unfolded Proteins: Folding and Collapse are Fundamentally Different

Patricia L. Clark et al.

JOURNAL OF MOLECULAR BIOLOGY (2020)

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Editorial Material Cell Biology

Clock regulation of protein secretion

Thomas P. Burris

NATURE CELL BIOLOGY (2020)

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Article Multidisciplinary Sciences

Valence and patterning of aromatic residues determine the phase behavior of prion-like domains

Erik W. Martin et al.

SCIENCE (2020)

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Article Multidisciplinary Sciences

Phase separation provides a mechanism to reduce noise in cells

A. Klosin et al.

SCIENCE (2020)

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Article Microbiology

Selective sequestration of signalling proteins in a membraneless organelle reinforces the spatial regulation of asymmetry in Caulobacter crescentus

Keren Lasker et al.

NATURE MICROBIOLOGY (2020)

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Article Chemistry, Physical

Biomolecular Phase Separation: From Molecular Driving Forces to Macroscopic Properties

Gregory L. Dignon et al.

Annual Review of Physical Chemistry (2020)

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Article Biochemistry & Molecular Biology

Condensation of Ded1p Promotes a Translational Switch from Housekeeping to Stress Protein Production

Christiane Iserman et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization

David W. Sanders et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules

Peiguo Yang et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Unblending of Transcriptional Condensates in Human Repeat Expansion Disease

Shaon Basu et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation

Jordina Guillen-Boixet et al.

CELL (2020)

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Article Chemistry, Physical

An analytical theory to describe sequence-specific inter-residue distance profiles for polyampholytes and intrinsically disordered proteins

Jonathan Huihui et al.

JOURNAL OF CHEMICAL PHYSICS (2020)

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Article Biochemistry & Molecular Biology

Flanking Regions Determine the Structure of the Poly-Glutamine in Huntingtin through Mechanisms Common among Glutamine-Rich Human Proteins

Annika Urbanek et al.

STRUCTURE (2020)

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Making the Case for Disordered Proteins and Biomolecular Condensates in Bacteria

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Relating sequence encoded information to form and function of intrinsically disordered proteins

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Fuzzy complexes: Specific binding without complete folding

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Effects of Linker Length and Transient Secondary Structure Elements in the Intrinsically Disordered Notch RAM Region on Notch Signaling

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A Period2 Phosphoswitch Regulates and Temperature Compensates Circadian Period

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