Co-translational assembly of mammalian nuclear multisubunit complexes.
Fiche publication
Date publication
avril 2019
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr TORA Laszlo
Tous les auteurs :
Kamenova I, Mukherjee P, Conic S, Mueller F, El-Saafin F, Bardot P, Garnier JM, Dembele D, Capponi S, Timmers HTM, Vincent SD, Tora L
Lien Pubmed
Résumé
Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling in a multisubunit complex are dispersed in the genome of eukaryotes, it is unclear how these protein complexes assemble. Here, we show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits, but lacking precise architectural details are built co-translationally. We demonstrate that dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). The lack of co-translational interaction can lead to degradation of the partner protein. Thus, protein synthesis and complex assembly are linked in building mammalian multisubunit complexes, suggesting that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will also advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.
Référence
Nat Commun. 2019 Apr 15;10(1):1740