Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex

Brian J. Conti, Johannes Elferich, Zhongying Yang, Ujwal Shinde, William Skach

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Eukaryotic secretory proteins cross the endoplasmic reticulum (ER) membrane through a protein-conducting channel contained within the ribosome- Sec61translocon complex (RTC). Using a zinc-finger sequence as a folding switch, we show that cotranslational folding of a secretory passenger inhibits translocation in canine ER microsomes and in human cells. Folding occurs within a cytosolically inaccessible environment, after ER targeting but before initiation of translocation, and it is most effective when the folded domain is 15-54 residues beyond the signal sequence. Under these conditions, substrate is diverted into cytosol at the stage of synthesis in which unfolded substrate enters the ER lumen. Moreover, the translocation block is reversed by passenger unfolding even after cytosol emergence. These studies identify an enclosed compartment within the assembled RTC that allows a short span of nascent chain to reversibly abort translocation in a substrate-specific manner.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalNature Structural and Molecular Biology
Volume21
Issue number3
DOIs
StatePublished - 2014

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Ribosomes
Endoplasmic Reticulum
Cytosol
Zinc Fingers
Protein Sorting Signals
Microsomes
Canidae
Proteins
Membranes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex. / Conti, Brian J.; Elferich, Johannes; Yang, Zhongying; Shinde, Ujwal; Skach, William.

In: Nature Structural and Molecular Biology, Vol. 21, No. 3, 2014, p. 228-235.

Research output: Contribution to journalArticle

Conti, Brian J. ; Elferich, Johannes ; Yang, Zhongying ; Shinde, Ujwal ; Skach, William. / Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex. In: Nature Structural and Molecular Biology. 2014 ; Vol. 21, No. 3. pp. 228-235.
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