Abstract
WE have determined the structure of a second human histocompati-bility glycoprotein, HLA-Aw68, by X-ray crystallography and refined it to a resolution of 2.6 Å. Overall, the structure is extremely similar to that of HLA-A2 (refs 1, 2; and M.A.S. et al., manuscript in preparation), although the 11 amino-acid substitutions at polymorphic residues3,4 in the antigen-binding cleft2 alter the detailed shape and electrostatic charge of that site. A prominent negatively charged pocket within the cleft extends underneath the α-helix of the α1-domain, providing a potential subsite for recognizing a positively charged side chain or peptide N terminus. Uninterpreted electron density, presumably representing an unknown 'antigen(s)', which seems to be different from that seen in the HLA-A2 structure1, occupies the cleft and extends into the negatively charged pocket in HLA-Aw68. The structures of HLA-Aw68 and HLA-A2 demonstrate how polymorphism creates and alters subsites (pockets) positioned to bind peptide side chains, thereby suggesting the structural basis for allelic specificity in foreign antigen binding.
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Garrett, T., Saper, M., Bjorkman, P. et al. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342, 692–696 (1989). https://doi.org/10.1038/342692a0
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DOI: https://doi.org/10.1038/342692a0
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