Cotranslational Stabilization of Sec62/63 within the ER Sec61 Translocon Is Controlled by Distinct Substrate-Driven Translocation Events

摘要: The ER Sec61 translocon is a large macromolecular machine responsible for partitioning secretory and membrane polypeptides into the lumen, cytosol, lipid bilayer. Because protein-conducting channel has been isolated in multiple membrane-derived complexes, we determined how nascent polypeptide modulates component associations during defined cotranslational translocation events. model substrate preprolactin (pPL) was principally with Sec61αβγ upon targeting, whereas higher-order complexes containing OST, TRAP, TRAM were stabilized following translocation. Blocking pPL by passenger domain folding favored stabilization of an alternate complex that contained Sec61, Sec62, Sec63. Moreover, Sec62/63 within occurred native endogenous substrates, such as prion protein, correlated delay translocation initiation. These data show contacts are ultimately controlled engaged chain resultant substrate-driven