computer modeling in molecular biology.pdf

7 Major Histocompatibility Complex Class I Protein-Peptide Interactions 179Figure 7-4 Figure 7-5Figure 7-4. Molecular model for the interaction of HLA-A*0201 with peptide. The peptide,shown as a pink tube with side chains in ball an stick representation, is sited in the antigenbinding cleft between the a-helices of the a1 and a2 domains (coloured red and green respectively).The domains coloured dark blue and light blue are a3 and P2-miroglobulin respectivelyand are membrane proximal in their orientation to the antigen presenting cell (APC).Both the N- and C-termini are heavily buried within the proteiy. In the 2.1 A structure ofHLA-B*2705 it has been demonstrated that 48% of the 2003 A2 of buried surface of theRRIKAITLK model peptide would be buried by the chelation of alanine residues from Pl-P3and P8-P9 with no residues built into positions P4-P7. This buried surface was increased to57% by the substitution of AlaP2 to ArgP2. This suggests that the predominant direct interactionsare at the termini and that the central bulge of the peptide is raised on a solvent bedto maximise its contact with the T-cell receptor (TCR).(Colour illustration see page XV).Figure 7-5. Side view of the model of HLA-A*0201 with peptide showing the asymmetry ofthe molecule. In the immunoglobulin-like a3 and P2-microglobulin domains the asymmetryof the packing gives rise to an atypical immunoglobulin (Ig) pairing. A slight shift in domaindisposition, with respect to that in HLA-A2, in the membrane proximal Ig-like domains hasbeen observed in the structures of HLA-B27 and H-2Kb.(Colour illustration see page XV).