Effect of Sec61 interaction with Mpd1 on endoplasmic reticulum-associated degradation

PLoS One. 2019 Jan 25;14(1):e0211180. doi: 10.1371/journal.pone.0211180. eCollection 2019.

Abstract

Proteins that misfold in the endoplasmic reticulum (ER) are transported back to the cytosol for ER-associated degradation (ERAD). The Sec61 channel is one of the candidates for the retrograde transport conduit. Channel opening from the ER lumen must be triggered by ERAD factors and substrates. Here we aimed to identify new lumenal interaction partners of the Sec61 channel by chemical crosslinking and mass spectrometry. In addition to known Sec61 interactors we detected ERAD factors including Cue1, Ubc6, Ubc7, Asi3, and Mpd1. We show that the CPY* ERAD factor Mpd1 binds to the lumenal Sec61 hinge region. Deletion of the Mpd1 binding site reduced the interaction between both proteins and caused an ERAD defect specific for CPY* without affecting protein import into the ER or ERAD of other substrates. Our data suggest that Mpd1 binding to Sec61 is a prerequisite for CPY* ERAD and confirm a role of Sec61 in ERAD of misfolded secretory proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum-Associated Degradation*
  • Protein Binding
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SEC Translocation Channels / genetics
  • SEC Translocation Channels / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Repressor Proteins
  • SEC Translocation Channels
  • SEC61 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • MPD1 protein, S cerevisiae
  • Protein Disulfide-Isomerases