Figure 1 - full size

 

Figure 1.
Figure 1. InsulinB bound to human HLA-DQ8 and pocket P9. (a) The surface of DQ8 with bound insulinB (yellow), viewed as seen by a T cell. Peptide side chains P1 glutamic acid, P4 tyrosine and P9 glutamic acid were buried in deep pockets, whereas P6 valine and P7 cysteine lay on shelf-like surfaces. The P4 pocket of DQ8 was nonpolar (white), whereas the P9 pocket was positively charged (blue). (Red surfaces were electrostatically negative.) (b) DQ8 P9 pocket with insulinB P9 glutamic acid (green) hydrogen-bonded to Arg76 , with Ala^57 replacing the common Asp57 . View was from the COOH-terminal end of the bound peptide (right end of a). DQ8 differed from I-A^g7 at chain residues 55 -57 proline-proline-alanine versus arginine-histidine-serine in I-A^g7. Hydrogen bonds are dashed red lines. (c) DR1 P9 pocket with Asp57 hydrogen-bonded to Arg76 and the hemagglutinin peptide P9 leucine (blue) in the electrostatically neutral pocket. (d) I-A^g7 P9 pocket with Ser57 and the GAD65 peptide P9 glutamic acid (purple) hydrogen-bonded to Arg76 and Ser57 (ref. 18). The chain helix (56 -57) in DQ8 was positioned closer to the P9 glutamic acid side chain and Arg76 than in I-A^g7. There is not enough space in the structure of DQ8 to replace Ala^57 with the larger side chain of a serine as in I-A^g7. (b -d) The chain helix residues 55 -57 shown on the left.

The above figure is reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2001, 2, 501-507) copyright 2001.