A single Sec61-complex functions as a protein-conducting channel

Biochim Biophys Acta. 2008 Dec;1783(12):2375-83. doi: 10.1016/j.bbamcr.2008.08.005. Epub 2008 Aug 20.

Abstract

During cotranslational translocation of proteins into the endoplasmic reticulum (ER) translating ribosomes bind to Sec61-complexes. Presently two models exist how these membrane protein complexes might form protein-conducting channels. While electron microscopic data suggest that a ring-like structure consisting of four Sec61-complexes build the channel, the recently solved crystal structure of a homologous bacterial protein complex led to the speculation that the actual tunnel is formed by just one individual Sec61-complex. Using protease protection assays together with quantitative immunoblotting we directly examined the structure of mammalian protein-conducting channels. We found that in native ER-membranes one single Sec61alpha-molecule is preferentially protected by a membrane bound ribosome, both, in the presence and absence of nascent polypeptides. In addition we present evidence that the nascent polypeptide destabilizes the ring-like translocation apparatus formed by four Sec61-complexes. Moreover, we found that after solubilization of ER-membranes a single Sec61-complex is sufficient to protect the nascent polypeptide chain against added proteases. Finally, we could show that this single Sec61-complex allows the movement of the nascent chain, when it has been released from the ribosome by puromycin treatment. Collectively, our data suggest that the active protein-conducting channel in the ER is formed by a single Sec61-complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dogs
  • Endoplasmic Reticulum, Rough / metabolism*
  • Gene Targeting
  • Ion Channels / metabolism*
  • Membrane Proteins / metabolism*
  • Pancreas / metabolism*
  • Peptide Chain Elongation, Translational
  • Protein Biosynthesis
  • Protein Transport
  • Ribosomes / metabolism
  • Ribosomes / ultrastructure*
  • SEC Translocation Channels
  • Transcription, Genetic

Substances

  • Ion Channels
  • Membrane Proteins
  • SEC Translocation Channels