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Specificity pockets for the side chains of peptide antigens in HLA-Aw68

Garrett, T. P. J. and Saper, M. A. and Bjorkman, P. J. and Strominger, J. L. and Wiley, D. C. (1989) Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature, 342 (6250). pp. 692-696. ISSN 0028-0836. doi:10.1038/342692a0.

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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 residues in the antigen-binding cleft 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 α_1-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 structure, 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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Bjorkman, P. J.0000-0002-2277-3990
Additional Information:© 1989 Nature Publishing Group. We thank Anastasia Haykov for technical assistance, Ted Jardetzky and Peter Parham for comments on the manuscript. and acknowledge support from the NIH and Howard Hughes Medical Institute. We also thank Ors Dean Mann (NIH), D. Michael Strong and James Wood (US Naval Research Unit) and Don Giard (MIT Cell Culture Facility) for provision of cells. Coordinates of HLA.Aw68 have been deposited in the Brookhaven Protein Data Bank (Accession no. 2HLA).
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:6250
Record Number:CaltechAUTHORS:20170406-090553081
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75787
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 16:41
Last Modified:15 Nov 2021 16:36

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