Functions of Intrinsically Disordered Regions

Intrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g.,...

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Main Authors: Linhu Xiao, Kun Xia
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/7/810
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author Linhu Xiao
Kun Xia
author_facet Linhu Xiao
Kun Xia
author_sort Linhu Xiao
collection DOAJ
description Intrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g., phosphorylation), enabling dynamic intermolecular interactions through conformational plasticity. Furthermore, IDRs drive liquid–liquid phase separation (LLPS) of biomacromolecules via multivalent interactions such as electrostatic attraction and pi–pi interactions, generating biomolecular condensates that are essential throughout the cellular lifecycle. These condensates separate intracellular space, forming a physical barrier to avoid interference between other molecules, thereby improving reaction specificity and efficiency. As a dynamically equilibrated process, LLPS formation and maintenance are regulated by multiple factors, endowing the condensates with rapid responsiveness to environmental cues and functional versatility in modulating diverse signaling cascades. Consequently, disruption of LLPS homeostasis can derail its associated biological processes, ultimately contributing to disease pathogenesis. Moreover, precisely because liquid–liquid phase separation (LLPS) is co-regulated by multiple factors, it may provide novel insights into the pathogenic mechanisms of disorders such as autism spectrum disorder (ASD), which result from the cumulative effects of multiple etiological factors.
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spelling doaj-art-4aa844b627f5401992fcbabf58897c7a2025-08-20T02:45:53ZengMDPI AGBiology2079-77372025-07-0114781010.3390/biology14070810Functions of Intrinsically Disordered RegionsLinhu Xiao0Kun Xia1MOE Key Lab of Rare Pediatric Diseases, School of Basic Medicine, Hengyang Medical College, University of South China, Hengyang 421001, ChinaMOE Key Lab of Rare Pediatric Diseases, School of Basic Medicine, Hengyang Medical College, University of South China, Hengyang 421001, ChinaIntrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g., phosphorylation), enabling dynamic intermolecular interactions through conformational plasticity. Furthermore, IDRs drive liquid–liquid phase separation (LLPS) of biomacromolecules via multivalent interactions such as electrostatic attraction and pi–pi interactions, generating biomolecular condensates that are essential throughout the cellular lifecycle. These condensates separate intracellular space, forming a physical barrier to avoid interference between other molecules, thereby improving reaction specificity and efficiency. As a dynamically equilibrated process, LLPS formation and maintenance are regulated by multiple factors, endowing the condensates with rapid responsiveness to environmental cues and functional versatility in modulating diverse signaling cascades. Consequently, disruption of LLPS homeostasis can derail its associated biological processes, ultimately contributing to disease pathogenesis. Moreover, precisely because liquid–liquid phase separation (LLPS) is co-regulated by multiple factors, it may provide novel insights into the pathogenic mechanisms of disorders such as autism spectrum disorder (ASD), which result from the cumulative effects of multiple etiological factors.https://www.mdpi.com/2079-7737/14/7/810intrinsically disordered regionsliquid–liquid phase separationmolecular recognition featurespost-translation modification
spellingShingle Linhu Xiao
Kun Xia
Functions of Intrinsically Disordered Regions
Biology
intrinsically disordered regions
liquid–liquid phase separation
molecular recognition features
post-translation modification
title Functions of Intrinsically Disordered Regions
title_full Functions of Intrinsically Disordered Regions
title_fullStr Functions of Intrinsically Disordered Regions
title_full_unstemmed Functions of Intrinsically Disordered Regions
title_short Functions of Intrinsically Disordered Regions
title_sort functions of intrinsically disordered regions
topic intrinsically disordered regions
liquid–liquid phase separation
molecular recognition features
post-translation modification
url https://www.mdpi.com/2079-7737/14/7/810
work_keys_str_mv AT linhuxiao functionsofintrinsicallydisorderedregions
AT kunxia functionsofintrinsicallydisorderedregions