Dislocation of type I membrane proteins from the er to the cytosol is sensitive to changes in redox potential

Domenico Tortorella, Craig M. Story, Johannes B. Huppa, Emmanuel J.H.J. Wiertz, Thomas R. Jones, Hidde L. Ploegh

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

The human cytomegalovirus (HCMV) gene products US2 and US11 dislocate major histocompatibility class I heavy chains from the ER and target them for proteasomal degradation in the cytosol. The dislocation reaction is inhibited by agents that affect intracellular redox potential and/or free thiol status, such as diamide and N-ethylmaleimide. Subcellular fractionation experiments indicate that this inhibition occurs at the stage of discharge from the ER into the cytosol. The T cell receptor α (TCR α) chain is also degraded by a similar set of reactions, yet in a manner independent of virally encoded gene products. Diamide and N-ethylmaleimide likewise inhibit the dislocation of the full-length TCR α chain from the ER, as well as a truncated, mutant version of TCR α chain that lacks cysteine residues. Cytosolic destruction of glycosylated, ER-resident type I membrane proteins, therefore, requires maintenance of a proper redox potential for the initial step of removal of the substrate from the ER environment.

Original languageEnglish
Pages (from-to)365-376
Number of pages12
JournalJournal of Cell Biology
Volume142
Issue number2
DOIs
StatePublished - 27 Jul 1998
Externally publishedYes

Keywords

  • Class I heavy chain
  • Degradation
  • Diamide
  • Human cytomegalovirus
  • TCR α chain

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