Molecular determinants of condensate composition

Abstract

Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces. In contrast, chemically specific recruitment is driven by complementary chemical interactions without the requirement for a persistent bound-state structure. We propose that site-specific and chemically specific interactions work together to determine the composition of condensates, facilitate biochemical reactions, and regulate enzymatic activities linked to metabolism, signaling, and gene expression. Characterizing the composition of condensates requires novel experimental and computational tools to identify and manipulate the molecular determinants guiding condensate recruitment. Advancing this research will deepen our understanding of how condensates regulate cellular functions, providing valuable insights into cellular physiology and organization.

Keywords: binding; biomolecular condensates; cellular organization; chemical specificity; disordered protein regions; phase separation; specificity.