Molecular structure in biomolecular condensates

TL;DR

This paper reviews recent evidence and debates on the molecular structures within biomolecular condensates, focusing on the roles of disordered domains and structured fibrils in phase separation.

Contribution

It synthesizes current viewpoints on the structural nature of low-complexity domains in condensates and highlights key open questions for future research.

Findings

Structures formed via multivalent domain-motif interactions are largely unchanged within condensates.

Discussions on whether low-complexity domains remain disordered or form amyloid-like structures.

Identification of outstanding questions to understand structure-function relationships.

Abstract

Evidence accumulated over the past decade provides support for liquid-liquid phase separation as the mechanism underlying the formation of biomolecular condensates, which include not only membraneless organelles such as nucleoli and RNA granules, but additional assemblies involved in transcription, translation and signaling. Understanding the molecular mechanisms of condensate function requires knowledge of the structures of their constituents. Current knowledge suggests that structures formed via multivalent domain-motif interactions remain largely unchanged within condensates. Two different viewpoints exist regarding structures of disordered low-complexity domains within condensates; one argues that low-complexity domains remain largely disordered in condensates and their multivalency is encoded in short motifs called stickers, while the other argues that the sequences form cross-beta structures resembling amyloid fibrils. We review these viewpoints and highlight outstanding questions that will inform structure-function relationships for biomolecular condensates.