Charge block-driven liquid-liquid phase separation - mechanism and biological roles.
J Cell Sci
; 137(11)2024 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-38855848
ABSTRACT
Liquid-liquid phase separation (LLPS) has increasingly been found to play pivotal roles in a number of intracellular events and reactions, and has introduced a new paradigm in cell biology to explain protein-protein and enzyme-ligand interactions beyond conventional molecular and biochemical theories. LLPS is driven by the cumulative effects of weak and promiscuous interactions, including electrostatic, hydrophobic and cation-π interactions, among polypeptides containing intrinsically disordered regions (IDRs) and describes the macroscopic behaviours of IDR-containing proteins in an intracellular milieu. Recent studies have revealed that interactions between 'charge blocks' - clusters of like charges along the polypeptide chain - strongly induce LLPS and play fundamental roles in its spatiotemporal regulation. Introducing a new parameter, termed 'charge blockiness', into physicochemical models of disordered polypeptides has yielded a better understanding of how the intrinsic amino acid sequence of a polypeptide determines the spatiotemporal occurrence of LLPS within a cell. Charge blockiness might also explain why some post-translational modifications segregate within IDRs and how they regulate LLPS. In this Review, we summarise recent progress towards understanding the mechanism and biological roles of charge block-driven LLPS and discuss how this new characteristic parameter of polypeptides offers new possibilities in the fields of structural biology and cell biology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Intrinsicamente Desordenadas
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article