Disordered regions of human eIF4B orchestrate a dynamic self-association landscape.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 Oct 2024
10 Oct 2024
Historique:
received:
21
06
2024
accepted:
03
10
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Eukaryotic translation initiation factor eIF4B is required for efficient cap-dependent translation, it is overexpressed in cancer cells, and may influence stress granule formation. Due to the high degree of intrinsic disorder, eIF4B is rarely observed in cryo-EM structures of translation complexes and only ever by its single structured RNA recognition motif domain, leaving the molecular details of its large intrinsically disordered region (IDR) unknown. By integrating experiments and simulations we demonstrate that eIF4B IDR orchestrates and fine-tunes an intricate transition from monomers to a condensed phase, in which large-size dynamic oligomers form before mesoscopic phase separation. Single-molecule spectroscopy combined with molecular simulations enabled us to characterize the conformational ensembles and underlying intra- and intermolecular dynamics across the oligomerization transition. The observed sensitivity to ionic strength and molecular crowding in the self-association landscape suggests potential regulation of eIF4B nanoscopic and mesoscopic behaviors such as driven by protein modifications, binding partners or changes to the cellular environment.
Identifiants
pubmed: 39384813
doi: 10.1038/s41467-024-53136-1
pii: 10.1038/s41467-024-53136-1
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Eukaryotic Initiation Factor-2B
0
eIF-4B
0
Eukaryotic Initiation Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8766Subventions
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : AJE20171239128
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-20-CE11-0007
Informations de copyright
© 2024. The Author(s).
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