Open AccessCotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly
Author(s) -
Krishnendu Khan,
Briana Long,
Camelia Baleanu-Gogonea,
Valentin Gogonea,
Gauravi Deshpande,
K.I. Vasu,
Paul L. Fox
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115799119
Subject(s) - ezrin , binding site , multiprotein complex , translation (biology) , microbiology and biotechnology , plasma protein binding , ribosome , biology , computational biology , cytoskeleton , biochemistry , messenger rna , rna , gene , cell
Significance Multiprotein complexes in mammalian cells are thought to form by interactions between domains of mature, fully folded proteins. However, in some cases interprotein interaction is obstructed by “buried” or inaccessible binding domains. One such example is the interaction between EBP50 and ezrin, proteins linking the plasma membrane and cytoskeleton; self-association of domains in ezrin masks the site recognized by EBP50. Here, we show EBP50 overcomes this obstacle by cotranslationally binding to nascent ezrin’s otherwise masked domain emerging from the translating ribosome. Our study extends the function of mRNA translation beyond “simple” generation of linear peptide chains that fold into mature proteins for subsequent complex assembly; additionally, cotranslation can facilitate interactions with sterically inaccessible domains to form functional multiprotein complexes.