Fig. 6.

A model for the assembly of the Derlin-1 complex during the retrotranslocation of MHC class I heavy chains. US11 initially targets glycosylated heavy chain (HC + CHO) to Derlin-1, resulting in a complex containing Derlin-1, US11, and HC plus CHO, which can be precipitated with antibodies to Derlin-1 (αDerlin-1). Substrate-bound Derlin-1 is then joined by a membrane complex containing VIMP, p97, and an E3 ligase (E3). The unknown ligase would be recruited to the complex in a similar way as Hrd1 and gp78. The final complex can be immunoprecipitated with antibodies to either VIMP or p97. A fraction of heavy chains (HC - CHO) associated with this complex has emerged into the cytosol because these lack carbohydrate chains, removed by a cytosolic glycanase.