FIGURE 7.

Model of features important for MARCH8 recognition of HLA-DR. Interaction between MARCH8 and HLA-DR is mediated by the sequence LFIYF, situated at the interfacial region between the TM hydrophobic core region and the cytosol (large arrow). Residues located in helical face 4 of DRβ (S, L, and T (small arrows)) are also important for MARCH8 interaction and are likely situated within the hydrophobic core. A significant interaction between a positively charged lysine on the exoplasmic side of the membrane is also indicated (large arrow). Close packing of the TM domains between DRα and DRβ is shown to involve glycine residues (16). Ubiquitination (Ub) occurs on a single lysine residue in the DRβ cytoplasmic tail (K). The dileucine motif (LL) at the C-terminal region of the DRβ cytoplasmic tail influences the efficiency of MARCH-mediated ubiquitination, probably by enhancing interactions with MARCK8 by internalization of HLA-DR molecules.