Determinants for intrinsically disordered protein recruitment into phase-separated protein condensates

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Multivalent interactions between amino acid residues of intrinsically disordered proteins (IDPs) drive phase separation of these proteins into liquid condensates, forming various membrane-less organelles in cells. These interactions between often biased residues of IDPs are also likely involved in selective recruitment of many other IDPs into condensates. However, determining factors for this IDP recruitment into protein condensates are not understood yet. Here, we quantitatively examined recruitment tendencies of various IDPs with different sequence compositions into IDP-clustered condensates both in vitro as well as in cells. Condensate-forming IDP scaffolds, recruited IDP clients, and phase separation conditions were carefully varied to find key factors for selective IDP partitioning in protein condensates. Regardless of scaffold sequences, charged residues in client IDPs assured potent IDP recruitment, likely via strong electrostatic interactions, where positive residues could further enhance recruitment, possibly with cation-pi interactions. Notably, poly-ethylene glycol, a widely used crowding reagent for in vitro phase separation, abnormally increased IDP recruitment, indicating the need for careful use of crowding conditions. Tyrosines of IDP clients also strongly participated in recruitment both in vitro and in cells. Lastly, we measured recruitment degrees by more conventional interactions between folded proteins instead of disordered proteins. Surprisingly, recruitment forces by an even moderate protein interaction (K-d similar to 5 mu M) were substantially stronger than those by natural IDP-IDP interactions. The present data offer valuable information on how cells might organize protein partitioning on various protein condensates.
Publisher
ROYAL SOC CHEMISTRY
Issue Date
2022-01
Language
English
Article Type
Article
Citation

CHEMICAL SCIENCE, v.13, no.2, pp.522 - 530

ISSN
2041-6520
DOI
10.1039/d1sc05672g
URI
http://hdl.handle.net/10203/291719
Appears in Collection
CH-Journal Papers(저널논문)
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