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Solid-state NMR methods to investigate biomolecular condensates, protein phase transition, phase separation and coacervates.

Jul 2026 · Biophysical Chemistry · Vol 338, pp. 107692 · 0 citations · 236 references
Medicine

TL;DR

An overview of solid-state NMR approaches that are readily applicable and potential methodological developments to investigate protein condensates and coacervates as well as to study protein phase separation and phase transitions are discussed.

Abstract

The formation of biomolecular condensates has been linked to a broad range of essential cellular processes, including immune signaling cascades, mRNA transport, and autophagy. Conversely, phase-separated condensates have also been associated with aberrant protein misfolding and subsequent aggregation in neurodegenerative disease-related processes. Protein phase separation and phase transitions involve the formation of heterogeneous and dynamic assemblies that can evolve into gel-like or semi-crystalline states, which are challenging to characterize using high-resolution structural biology techniques. Solid-state nuclear magnetic resonance (NMR) spectroscopy now offers a broad arsenal of methods to probe the structural and dynamic features of viscous condensates, elastic solids, coacervates and rigid protein assemblies. This review provides an overview of solid-state NMR approaches that are readily applicable and discusses potential methodological developments to investigate protein condensates and coacervates as well as to study protein phase separation and phase transitions.

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