Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein

Heather Sadlish, David Pitonzo, Arthur E. Johnson, William R. Skach

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61α and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61α cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61α from different molecular environments. Thus, AQP4 integration by Sec61α involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.

Original languageEnglish (US)
Pages (from-to)870-878
Number of pages9
JournalNature Structural and Molecular Biology
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2005

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein'. Together they form a unique fingerprint.

  • Cite this