Issue 48, 2022

Chemical tools for study and modulation of biomolecular phase transitions

Abstract

Biomolecular phase transitions play an important role in organizing cellular processes in space and time. Methods and tools for studying these transitions, and the intrinsically disordered proteins (IDPs) that often drive them, are typically less developed than tools for studying their folded protein counterparts. In this perspective, we assess the current landscape of chemical tools for studying IDPs, with a specific focus on protein liquid–liquid phase separation (LLPS). We highlight methodologies that enable imaging and spectroscopic studies of these systems, including site-specific labeling with small molecules and the diverse range of capabilities offered by inteins and protein semisynthesis. We discuss strategies for introducing post-translational modifications that are central to IDP and LLPS function and regulation. We also investigate the nascent field of noncovalent small-molecule modulators of LLPS. We hope that this review of the state-of-the-art in chemical tools for interrogating IDPs and LLPS, along with an associated perspective on areas of unmet need, can serve as a valuable and timely resource for these rapidly expanding fields of study.

Graphical abstract: Chemical tools for study and modulation of biomolecular phase transitions

Article information

Article type
Perspective
Submitted
03 Sep 2022
Accepted
21 Nov 2022
First published
21 Nov 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 14226-14245

Chemical tools for study and modulation of biomolecular phase transitions

R. F. Berkeley and G. T. Debelouchina, Chem. Sci., 2022, 13, 14226 DOI: 10.1039/D2SC04907D

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