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

Brian J. Conti, Prasanna K. Devaraneni, Zhongying Yang, Larry David, William Skach

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)269-283
Number of pages15
JournalMolecular Cell
Volume58
Issue number2
DOIs
StatePublished - Apr 16 2015

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Membranes
Peptides
Lipid Bilayers
Cytosol
Proteins
Prion Proteins
preprolactin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cotranslational Stabilization of Sec62/63 within the ER Sec61 Translocon Is Controlled by Distinct Substrate-Driven Translocation Events. / Conti, Brian J.; Devaraneni, Prasanna K.; Yang, Zhongying; David, Larry; Skach, William.

In: Molecular Cell, Vol. 58, No. 2, 16.04.2015, p. 269-283.

Research output: Contribution to journalArticle

Conti, Brian J. ; Devaraneni, Prasanna K. ; Yang, Zhongying ; David, Larry ; Skach, William. / Cotranslational Stabilization of Sec62/63 within the ER Sec61 Translocon Is Controlled by Distinct Substrate-Driven Translocation Events. In: Molecular Cell. 2015 ; Vol. 58, No. 2. pp. 269-283.
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