3hla

From Proteopedia

Revision as of 15:43, 15 February 2008

SPECIFICITY POCKETS FOR THE SIDE CHAINS OF PEPTIDE ANTIGENS IN HLA-AW68

Overview

The three-dimensional structure of the human histocompatibility antigen, HLA-A2 was determined at 3.5 A resolution by a combination of isomorphous, replacement and iterative real-space averaging of two crystal forms. The, monoclinic crystal form has now been refined by least-squares methods to, an R-factor of 0.169 for data from 6 to 2.6 A resolution. A superposition, of the structurally similar domains found in the heterodimer, alpha 1 onto, alpha 2 and alpha 3 onto beta 2m, as well as the latter pair onto the, ancestrally related immunoglobulin constant domain, reveals that, differences are mainly in the turn regions. Structural features of the, alpha 1 and alpha 2 domains, such as conserved salt-bridges that, contribute to stability, specific loops that form contacts with other, domains, and the antigen-binding groove formed from two adjacent helical, regions on top of an eight-stranded beta-sheet, are analyzed. The, interfaces between the domains, especially those between beta 2m and the, HLA heavy chain presumably involved in beta 2m exchange and heterodimer, assembly, are described in detail. A detailed examination of the binding, groove confirms that the solvent-accessible amino acid side-chains that, are most polymorphic in mouse and human alleles fill up the central and, widest portion of the binding groove, while conserved side-chains are, clustered at the narrower ends of the groove. Six pockets or sub-sites in, the antigen-binding groove, of diverse shape and composition, appear, suited for binding side-chains from antigenic peptides. Three pockets, contain predominantly non-polar atoms; but others, especially those at the, extreme ends of the groove, have clusters of polar atoms in close, proximity to the "extra" electron density in the binding site. A possible, role for beta 2m in stabilizing permissible peptide complexes during, folding and assembly is presented.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]

About this Structure

3HLA is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution., Saper MA, Bjorkman PJ, Wiley DC, J Mol Biol. 1991 May 20;219(2):277-319. PMID:2038058

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