Publication Date

5-1-2023

Journal

Trends in Biochemical Sciences

DOI

10.1016/j.tibs.2023.01.004

PMID

36754681

PMCID

PMC10106370

PubMedCentral® Posted Date

5-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Proteins, Intrinsically Disordered Proteins, LLPS, structure, condensate, composition, expression

Abstract

Intrinsically disordered regions (IDRs) are especially enriched among proteins that regulate chromatin and transcription. As a result, mechanisms that influence specificity of IDR-driven interactions have emerged as exciting unresolved issues for understanding gene regulation. We review the molecular elements frequently found within IDRs that confer regulatory specificity. In particular, we summarize the differing roles of disordered low-complexity regions (LCRs) and short linear motifs (SLiMs) towards selective nuclear regulation. Examination of IDR-driven interactions highlights SLiMs as organizers of selectivity, with widespread roles in gene regulation and integration of cellular signals. Analysis of recurrent interactions between SLiMs and folded domains suggests diverse avenues for SLiMs to influence phase-separated condensates and highlights opportunities to manipulate these interactions for control of biological activity.

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