Fig. 4. Interactions within the MHC-I Peptide Loading Complex (PLC).

Panels A and B represent the structure of tapasin (grey) and its predicted interaction with an HLA class I molecule (green). In panel A tapasin is depicted in a space filling model and the multi residue mutations of tapasin that defined its interaction with MHC-I (TN3, TN4, TN6 and TN7) are indicated in pink, red and orange. The HLA class I molecule is presented as a ribbon diagram and position 86, the N-glycosylation site at the end of the α1 helix is indicated. In panel B tapasin is presented as a ribbon diagram and the HLA molecule is depicted as a space filling model. Published mutations that were defined as interfering with the MHC-I/PLC interaction are indicated. Panels C and D represent different views of an inferred model of the subcomplex of the PLC that includes MHC-I (green), tapasin (grey), calreticulin (yellow) and ERp57 (light blue). The pink, red and orange areas represent the MHC-I interaction sites on tapasin depicted in panel A. In both panels C and D the residue numbers in light blue define the site on ERp57 where the extended proline-rich P domain of calreticulin interacts based on mutagenesis. In panel D the residue numbers in dark blue define the site on calreticulin that binds to the monoglucosylated N-linked glycan on the MHC-I heavy chain. The MHC-I peptide binding groove as depicted is derived from a crystallographic structure that contains a bound peptide. Within the PLC this structure is undoubtedly modified, probably with a displaced segment of the α2 helix, as observed in the TAPBPR/MHC-I structures discussed in the text. (reproduced with permission from Dong, Wearsch et al., 2009).