4.6 Review

Roc, the G-domain of the Parkinson's disease-associated protein LRRK2

Related references

Note: Only part of the references are listed.
Article Multidisciplinary Sciences

Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2

Ranjan K. Singh et al.

Summary: Mutations in the LRRK2 gene are a leading cause of Parkinson's disease, while overactivation of LRRK2 is associated with idiopathic form of the disease. Researchers have identified and characterized nanobodies that can bind to different domains of LRRK2 and inhibit or activate its activity. These nanobodies act through an allosteric inhibitor mechanism and provide potential therapeutic strategies for Parkinson's disease.

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

Article Biochemistry & Molecular Biology

LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains

Jui-Hung H. Weng et al.

Summary: This study generated a comprehensive dynamic allosteric portrait of the C-terminal domains of LRRK2 using HDX-MS and MD simulations. It identified two helices that regulate LRRK2 conformation and function, providing potential sites for pharmacological intervention.

PLOS BIOLOGY (2022)

Article Multidisciplinary Sciences

Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab10 and RILPL1 proteins

Yuriko Sobu et al.

Summary: Mutations that activate LRRK2 protein kinase lead to Parkinson's disease and hinder cilia formation. LRRK2 kinase activity decreases the probability of ciliation and increases the percentage of cilia lost upon serum addition. Rab10 and RILPL1 proteins play crucial roles in these processes.

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

Article Biology

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain

Shahzad S. Khan et al.

Summary: Activating mutations of LRRK2 cause Parkinson's disease and result in cilia loss. The loss of cilia is associated with phosphorylation of Rab GTPases, defects in astrocytes, and dysregulation of the Hedgehog signaling pathway in the nigrostriatal pathway.

ELIFE (2021)

Article Biology

LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

Herschel S. Dhekne et al.

Summary: The study reveals that RILPL2 binds preferentially to LRRK2-phosphorylated Rab8A and Rab10, providing insights into the molecular basis of LRRK2 pathogenesis.

LIFE SCIENCE ALLIANCE (2021)

Article Biochemistry & Molecular Biology

Allosteric Inhibition of Parkinson's-Linked LRRK2 by Constrained Peptides

Leah G. Helton et al.

Summary: Dimerization of LRRK2 can be inhibited by specific constrained peptides, leading to decreased kinase activity, reduced ROS production, and inhibition of PD-related apoptosis in primary cortical neurons. Unlike other inhibitors, these peptides do not affect the cellular localization of LRRK2.

ACS CHEMICAL BIOLOGY (2021)

Article Biochemistry & Molecular Biology

Structural analysis of the full-length human LRRK2

Alexander Myasnikov et al.

Summary: Mutations in LRRK2 are commonly associated with Parkinson's disease. This study provides insights into the physiological and pathological roles of LRRK2, and establishes a structural template for future therapeutic interventions in PD. The high-resolution structures of full-length human LRRK2 and COR-mediated LRRK2 dimers reveal key elements for rationalizing disease-causing mutations and potential targets for inhibitors.
Review Clinical Neurology

LRRK2 in Parkinson disease: challenges of clinical trials

Eduardo Tolosa et al.

NATURE REVIEWS NEUROLOGY (2020)

Article Biochemistry & Molecular Biology

Allosteric modulation of the GTPase activity of a bacterial LRRK2 homolog by conformation-specific Nanobodies

Margaux Leemans et al.

BIOCHEMICAL JOURNAL (2020)

Article Biochemistry & Molecular Biology

The In Situ Structure of Parkinson's Disease-Linked LRRK2

Reika Watanabe et al.

Article Multidisciplinary Sciences

Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity

An Phu Tran Nguyen et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Multidisciplinary Sciences

Structure of LRRK2 in Parkinson's disease and model for microtubule interaction

C. K. Deniston et al.

NATURE (2020)

Review Biochemistry & Molecular Biology

LRRK2 links genetic and sporadic Parkinson's disease

Jillian H. Kluss et al.

BIOCHEMICAL SOCIETY TRANSACTIONS (2019)

Article Biochemistry & Molecular Biology

Parkinson's disease-associated mutations in the GTPase domain of LRRK2 impair its nucleotide-dependent conformational dynamics

Chun-Xiang Wu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

Article Pharmacology & Pharmacy

Recent Developments in LRRK2-Targeted Therapy for Parkinson's Disease

Ye Zhao et al.

DRUGS (2019)

Article Biochemistry & Molecular Biology

Structure and nucleotide-induced conformational dynamics of the Chlorobium tepidum Roco protein

Egon Deyaert et al.

BIOCHEMICAL JOURNAL (2019)

Article Biochemistry & Molecular Biology

The Parkinson's disease-associated mutation N1437H impairs conformational dynamics in the G domain of LRRK2

Xiaorong Huang et al.

FASEB JOURNAL (2019)

Article Multidisciplinary Sciences

LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson's disease patients

Daniel Ysselstein et al.

NATURE COMMUNICATIONS (2019)

Article Multidisciplinary Sciences

Molecular mechanism of ATP versus GTP selectivity of adenylate kinase

Per Rogne et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Biochemistry & Molecular Biology

Revisiting the Roco G-protein cycle

Susanne Terheyden et al.

BIOCHEMICAL JOURNAL (2015)

Article Cell Biology

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

Reina N. Fuji et al.

SCIENCE TRANSLATIONAL MEDICINE (2015)

Article Biochemistry & Molecular Biology

Novel LRRK2 GTP-binding inhibitors reduced degeneration in Parkinson's disease cell and mouse models

Tianxia Li et al.

HUMAN MOLECULAR GENETICS (2014)

Article Multidisciplinary Sciences

Parkinson disease-associated mutation R1441H in LRRK2 prolongs the active state of its GTPase domain

Jingling Liao et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Multidisciplinary Sciences

Dynamic architecture of a protein kinase

Christopher L. McClendon et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Multidisciplinary Sciences

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

Alexandria Beilina et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Biochemistry & Molecular Biology

GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2

Alice Biosa et al.

HUMAN MOLECULAR GENETICS (2013)

Article Biochemistry & Molecular Biology

LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6

Daniel C. Berwick et al.

HUMAN MOLECULAR GENETICS (2012)

Article Biochemistry & Molecular Biology

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

Martin C. Herzig et al.

HUMAN MOLECULAR GENETICS (2011)

Article Biochemistry & Molecular Biology

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

Byoung Dae Lee et al.

NATURE MEDICINE (2010)

Review Clinical Neurology

LRRK2 and neurodegeneration

Gabriel Santpere et al.

ACTA NEUROPATHOLOGICA (2009)

Article Biochemistry & Molecular Biology

Characterization of a Ras Mutant with Identical GDP- and GTP-Bound Structures

Bradley Ford et al.

BIOCHEMISTRY (2009)

Article Biotechnology & Applied Microbiology

LRRK2 p.G2019S mutation is not common among Alzheimer's disease patients in Brazil

Cintia Barros Santos-Reboucas et al.

DISEASE MARKERS (2009)

Article Biochemistry & Molecular Biology

Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment

Christian L. Klein et al.

JOURNAL OF NEUROCHEMISTRY (2009)

Article Clinical Neurology

Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease

Owen A. Ross et al.

ANNALS OF NEUROLOGY (2008)

Article Oncology

LRRK2 regulates synaptic vesicle endocytosis

Narae Shin et al.

EXPERIMENTAL CELL RESEARCH (2008)

Article Biochemistry & Molecular Biology

Intramolecular Activation Mechanism of theDictyosteliumLRRK2 Homolog Roco Protein GbpC

Wouter N. van Egmond et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Article Biochemistry & Molecular Biology

LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity

Mahaboobi Jaleel et al.

BIOCHEMICAL JOURNAL (2007)

Article Biochemistry & Molecular Biology

Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity

Andrew B. West et al.

HUMAN MOLECULAR GENETICS (2007)

Article Clinical Neurology

Localization of LRRK2 to membranous and vesicular structures in mammalian brain

Saskia Biskup et al.

ANNALS OF NEUROLOGY (2006)

Article Neurosciences

Kinase activity is required for the toxic effects of mutant LRRK2/dardarin

Elisa Greggio et al.

NEUROBIOLOGY OF DISEASE (2006)

Article Biochemistry & Molecular Biology

The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity

CJ Gloeckner et al.

HUMAN MOLECULAR GENETICS (2006)

Article Multidisciplinary Sciences

Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity

AB West et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Article Biochemistry & Molecular Biology

Roc, a Ras/GTPase domain in complex proteins

L Bosgraaf et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2003)

Article Clinical Neurology

A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1

M Funayama et al.

ANNALS OF NEUROLOGY (2002)

Review Multidisciplinary Sciences

Signal transduction - The guanine nucleotide-binding switch in three dimensions

IR Vetter et al.

SCIENCE (2001)