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A membrane protein required for dislocation of misfolded proteins from the ER.

After insertion into the endoplasmic reticulum (ER), proteins that fail to fold there are destroyed. Through a process termed dislocation such misfolded proteins arrive in the cytosol, where ubiquitination, deglycosylation and finally proteasomal proteolysis dispense with the unwanted polypeptides. The machinery involved in the extraction of misfolded proteins from the ER is poorly defined. The human cytomegalovirus-encoded glycoproteins US2 and US11 catalyse the dislocation of class I major histocompatibility complex (MHC) products, resulting in their rapid degradation. Here we show that US11 uses its transmembrane domain to recruit class I MHC products to a human homologue of yeast Der1p, a protein essential for the degradation of a subset of misfolded ER proteins. We show that this protein, Derlin-1, is essential for the degradation of class I MHC molecules catalysed by US11, but not by US2. We conclude that Derlin-1 is an important factor for the extraction of certain aberrantly folded proteins from the mammalian ER.

Pubmed ID: 15215855


  • Lilley BN
  • Ploegh HL



Publication Data

June 24, 2004

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Catalysis
  • Cell Line, Tumor
  • Endoplasmic Reticulum
  • Histocompatibility Antigens Class I
  • Humans
  • Membrane Glycoproteins
  • Membrane Proteins
  • Molecular Sequence Data
  • Protein Binding
  • Protein Denaturation
  • Protein Folding
  • Protein Transport
  • RNA-Binding Proteins
  • Viral Envelope Proteins
  • Viral Proteins