Intrinsically disordered regions are poised to act as sensors of cellular chemistry

David Moses; Garrett M Ginell; Alex S Holehouse; Shahar Sukenik

doi:10.1016/j.tibs.2023.08.001

Intrinsically disordered regions are poised to act as sensors of cellular chemistry

Trends Biochem Sci. 2023 Dec;48(12):1019-1034. doi: 10.1016/j.tibs.2023.08.001. Epub 2023 Aug 31.

Authors

David Moses¹, Garrett M Ginell², Alex S Holehouse³, Shahar Sukenik⁴

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, Merced, CA, USA.
² Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates (CBC), Washington University in St. Louis, St. Louis, MO, USA.
³ Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates (CBC), Washington University in St. Louis, St. Louis, MO, USA. Electronic address: [email protected].
⁴ Department of Chemistry and Biochemistry, University of California, Merced, CA, USA; Quantitative Systems Biology Program, University of California, Merced, CA, USA. Electronic address: [email protected].

Abstract

Intrinsically disordered proteins and protein regions (IDRs) are abundant in eukaryotic proteomes and play a wide variety of essential roles. Instead of folding into a stable structure, IDRs exist in an ensemble of interconverting conformations whose structure is biased by sequence-dependent interactions. The absence of a stable 3D structure, combined with high solvent accessibility, means that IDR conformational biases are inherently sensitive to changes in their environment. Here, we argue that IDRs are ideally poised to act as sensors and actuators of cellular physicochemistry. We review the physical principles that underlie IDR sensitivity, the molecular mechanisms that translate this sensitivity to function, and recent studies where environmental sensing by IDRs may play a key role in their downstream function.

Keywords: biosensors; cellular environment; intrinsically disordered proteins; intrinsically disordered regions; signaling.

Publication types

Review

MeSH terms

Intrinsically Disordered Proteins* / metabolism
Protein Conformation
Protein Domains

Substances

Intrinsically Disordered Proteins

Grants and funding

R35 GM137926/GM/NIGMS NIH HHS/United States