Titel
Protein compactness and interaction valency define the architecture of a biomolecular condensate across scales
Autor*in
Autor*in
Roman G Efremov
MM Shemyakin and Yu A Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
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Abstract
Non-membrane-bound biomolecular condensates have been proposed to represent an important mode of subcellular organization in diverse biological settings. However, the fundamental principles governing the spatial organization and dynamics of condensates at the atomistic level remain unclear. The Saccharomyces cerevisiae Lge1 protein is required for histone H2B ubiquitination and its N-terminal intrinsically disordered fragment (Lge1₁₋₈₀) undergoes robust phase separation. This study connects single- and multi-chain all-atom molecular dynamics simulations of Lge1₁₋₈₀with the in vitro behavior of Lge1₁₋₈₀ condensates. Analysis of modeled protein-protein interactions elucidates the key determinants of Lge1₁₋₈₀ condensate formation and links configurational entropy, valency, and compactness of proteins inside the condensates. A newly derived analytical formalism, related to colloid fractal cluster formation, describes condensate architecture across length scales as a function of protein valency and compactness. In particular, the formalism provides an atomistically resolved model of Lge1₁₋₈₀ condensates on the scale of hundreds of nanometers starting from individual protein conformers captured in simulations. The simulation-derived fractal dimensions of condensates of Lge1₁₋₈₀ and its mutants agree with their in vitro morphologies. The presented framework enables a multiscale description of biomolecular condensates and embeds their study in a wider context of colloid self-organization.
Stichwort
General Immunology and MicrobiologyGeneral Biochemistry, Genetics and Molecular BiologyGeneral MedicineGeneral Neuroscience
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
eLife
Band
12
ISSN
2050-084X
Erscheinungsdatum
2023
Publication
eLife Sciences Publications, Ltd
Projekt
Kod / Identifikator
P 30550
Projekt
Kod / Identifikator
P 30680-B21
Projekt
Erscheinungsdatum
2023
Zugänglichkeit
Rechteangabe
(c) Polyansky, Gallego et al.

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