Figure 6.

Model for dislocation of class I heavy chains by US2 and US11. (a) The dislocation reaction is initiated by binding of US2 or US11 to the heavy chain with most intermolecular contacts within the ER lumen. (b) Once in the translocon, the class I heavy chain unfolds. The light chain of class I and MHC-bound peptide may then dissociate within the ER. Cytosolic factors (black box) bind to the cytosolic tail of the class I heavy chain and aid in its extraction. (c) N-glycanase (gray box) attacks the glycan when it emerges into the cytosol. Proteasome cleaves the class I heavy chain. (d) In the presence of proteasomal inhibitors, a portion of the heavy chain is deflected into the cytosol directly and accumulates as a deglycosylated intermediate.