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Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions

Chong, Shasha and Mir, Mustafa (2021) Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions. Journal of Molecular Biology, 433 (12). Art. No. 166724. ISSN 0022-2836. doi:10.1016/j.jmb.2020.11.023.

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A substantial portion of the proteome consists of intrinsically disordered regions (IDRs) that do not fold into well-defined 3D structures yet perform numerous biological functions and are associated with a broad range of diseases. It has been a long-standing enigma how different IDRs successfully execute their specific functions. Further putting a spotlight on IDRs are recent discoveries of functionally relevant biomolecular assemblies, which in some cases form through liquid-liquid phase separation. At the molecular level, the formation of biomolecular assemblies is largely driven by weak, multivalent, but selective IDR-IDR interactions. Emerging experimental and computational studies suggest that the primary amino acid sequences of IDRs encode a variety of their interaction behaviors. In this review, we focus on findings and insights that connect sequence-derived features of IDRs to their conformations, propensities to form biomolecular assemblies, selectivity of interaction partners, functions in the context of physiology and disease, and regulation of function. We also discuss directions of future research to facilitate establishing a comprehensive sequence-function paradigm that will eventually allow prediction of selective interactions and specificity of function mediated by IDRs.

Item Type:Article
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Chong, Shasha0000-0002-5372-311X
Mir, Mustafa0000-0001-8280-2821
Additional Information:© 2020 Elsevier. Received 29 June 2020, Revised 14 November 2020, Accepted 19 November 2020, Available online 26 November 2020. We thank Robert Tjian and John Ferrie for critical reading of the manuscript. CRediT authorship contribution statement. Shasha Chong: Supervision, Conceptualization, Investigation, Writing - original draft, Visualization. Mustafa Mir: Investigation, Writing - review & editing, Visualization. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Subject Keywords:intrinsically disordered regions; interactions; biomolecular assemblies; sequence; function
Issue or Number:12
Record Number:CaltechAUTHORS:20210902-234004411
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Official Citation:Shasha Chong, Mustafa Mir, Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions, Journal of Molecular Biology, Volume 433, Issue 12, 2021, 166724, ISSN 0022-2836,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110715
Deposited By: George Porter
Deposited On:07 Sep 2021 18:05
Last Modified:07 Sep 2021 18:05

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