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EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.

Terminally misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently cleared by the ER-associated degradation (ERAD) pathway. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however, the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined. EDEM1 (ER degradation-enhancing alpha-mannosidase-like 1 protein) has been proposed to play a role in ERAD substrate signaling or recognition. We show that EDEM1 specifically binds nonnative proteins in a glycan-independent manner. Inhibition of mannosidase activity with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDEM1 substrate binding but diminished its association with the ER membrane adaptor protein SEL1L. These results support a model whereby EDEM1 binds nonnative proteins and uses its mannosidase-like domain to target aberrant proteins to the ER membrane dislocation and ubiquitination complex containing SEL1L.

Pubmed ID: 19524542


  • Cormier JH
  • Tamura T
  • Sunryd JC
  • Hebert DN


Molecular cell

Publication Data

June 12, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: CA79864
  • Agency: NCI NIH HHS, Id: R01 CA079864
  • Agency: NCI NIH HHS, Id: R01 CA079864-10

Mesh Terms

  • Binding Sites
  • Carbohydrate Metabolism
  • Cell Line
  • Endoplasmic Reticulum
  • Glycoproteins
  • Humans
  • Mannose
  • Membrane Proteins
  • Polysaccharides
  • Protein Folding
  • Protein Structure, Tertiary
  • Proteins
  • Substrate Specificity