1akj

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spinqualitylabelsall models 1akj, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

COMPLEX OF THE HUMAN MHC CLASS I GLYCOPROTEIN HLA-A2 AND THE T CELL CORECEPTOR CD8

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], CD8 deficiency, familial OMIM:[186910], Hypoproteinemia, hypercatabolic OMIM:[109700], Megakaryoblastic leukemia, acute OMIM:[606078], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]

About this Structure

1AKJ is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus. Full crystallographic information is available from OCA.

Reference

Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2., Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK, Nature. 1997 Jun 5;387(6633):630-4. PMID:9177355

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