Fig. 4: The locked and unlocked states of the A and F pockets of A2.

a Ribbon diagram of the dsA2/peptide_free-1 crystal structure, showing electron density from a 2mF_o–DF_c map for the water molecules (gray) and the EDO molecules (green) in the peptide-binding groove at a contour level of 1σ. b Close-up of the A pocket in the locked (cyan, from the dsA2/GM structure) and the unlocked (gold, from the peptide-free structure) states. In the unlocked state, the hydrogen bond between Tyr99 and His70 is broken and the side chains of His70 and Phe9 move into the peptide-binding groove, whereas the side chain of Tyr99 moves downwards. c Systematic analysis of the distance distribution between the OH atom on Tyr99 and the closest nitrogen atom on the imidazole side chain of His70 for all peptide-loaded HLA-A0201 molecules observed in the PDB. The histogram shows that >90% of the deposited structures contain a hydrogen bond between His70 and Tyr99. d, e Two alternate hydrogen bond networks that are formed as a result of the presence of the methionine side chain in the F pocket are seen in each dsA2/GM₂ molecule. This leads to conformational changes in the side chains of residues His74 and Phe9.