The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier

J Biol Chem. 2020 Feb 14;295(7):2125-2134. doi: 10.1074/jbc.RA119.010378. Epub 2019 Dec 17.


The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61β subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions. Loss in Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C terminus is juxtaposed to the key gating module of Sec61p/Sec61α, and we hypothesize it is important for gating the ER translocon. The ER stress response was found to be constitutively induced in two temperature-sensitive sss1 mutants (sss1ts ) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1ts cells to grow at 37 °C suggests the ER permeability barrier to be compromised in these mutants. We propose the extreme C terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier.

Keywords: Sec61 complex; Sec61p/Sec61α; Sss1p/Sec61γ; endoplasmic reticulum (ER); endoplasmic reticulum stress (ER stress); endoplasmic reticulum–associated protein degradation (ERAD); gating; translocation; translocon gating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Endoplasmic Reticulum / genetics*
  • Endoplasmic Reticulum Stress / genetics
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Mutation / genetics
  • Permeability
  • Protein Biosynthesis / genetics*
  • Protein Transport / genetics
  • SEC Translocation Channels / chemistry
  • SEC Translocation Channels / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*


  • Multiprotein Complexes
  • SEC Translocation Channels
  • SEC61 protein, S cerevisiae
  • SSS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Associated data

  • PDB/2WWA