Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 19, Pages 6586-6593Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.REV120.012413
Keywords
protein folding; protein denaturation; protein chemistry; intrinsically disordered protein; mutagenesis; folding kinetics; mutagenesis; transition state; reaction mechanism
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Funding
- Italian Ministero dell'Istruzione dell'Universitae della Ricerca (Progetto di Interesse Invecchiamento)
- Sapienza University of Rome [B52F16003410005, RP11715C34AEAC9B, RM1181641C2C24B9]
- Associazione Italiana per la Ricerca sul Cancro Individual Grant MFAG 2016 [18701]
- Istituto Pasteur Italia Teresa Ariaudo Research Project 2018
- Swedish Research Council [2016-04965]
- Swedish Research Council [2016-04965] Funding Source: Swedish Research Council
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Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed ?templated folding,? whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding.
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