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Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, United States; The Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, United States.
Journal of Molecular Biology
|November 28, 2020
Summary
Intrinsically disordered regions (IDRs) lack fixed structures but perform vital functions and cause diseases. Their amino acid sequences dictate interactions, assembly formation, and function, offering a new paradigm for understanding biological complexity.
Area of Science:
- Biochemistry and Molecular Biology
- Genomics and Proteomics
Background:
- A significant part of the proteome comprises intrinsically disordered regions (IDRs) lacking defined 3D structures.
- IDRs are crucial for various biological functions and implicated in numerous diseases.
- The precise mechanisms by which IDRs execute specific functions remain largely enigmatic.
Purpose of the Study:
- To review current findings linking IDR sequence features to their conformational states, assembly formation, and interaction selectivity.
- To explore the role of IDRs in physiological and disease contexts, including their regulatory mechanisms.
- To outline future research directions for a comprehensive sequence-function paradigm in IDRs.
Main Methods:
- Literature review of experimental and computational studies on intrinsically disordered regions.
- Analysis of sequence-derived features and their correlation with IDR properties.
- Synthesis of current knowledge on IDR function, regulation, and disease association.
Main Results:
- IDR primary amino acid sequences encode diverse interaction behaviors, influencing conformations and biomolecular assembly formation.
- Weak, multivalent, yet selective IDR-IDR interactions drive the formation of functional biomolecular assemblies, including those via liquid-liquid phase separation.
- Sequence features dictate IDR interaction partner selectivity, functional roles in health and disease, and regulatory mechanisms.
Conclusions:
- Understanding the sequence-derived properties of IDRs is key to deciphering their functional diversity and roles in disease.
- Establishing a comprehensive sequence-function paradigm for IDRs will enable prediction of their selective interactions and specific functions.
- Future research should focus on integrating sequence information to predict IDR behavior and function, advancing fields from basic biology to therapeutic development.
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