2jcc

From Proteopedia

---

Revision as of 20:47, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 2jcc, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

AH3 RECOGNITION OF MUTANT HLA-A2 W167A

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The keystone of the adaptive immune response is T cell receptor (TCR), recognition of peptide presented by major histocompatibility complex, (pMHC) molecules. The crystal structure of AHIII TCR bound to MHC, HLA-A2, showed a large interface with an atypical binding orientation. MHC, mutations in the interface of the proteins were tested for changes in TCR, recognition. From the range of responses observed, three representative, HLA-A2 mutants, T163A, W167A, and K66A, were selected for further study., Binding constants and co-crystal structures of the AHIII TCR and the three, mutants were determined. K66 in HLA-A2 makes contacts with both peptide, and TCR, and has been identified as a critical residue for recognition by, numerous TCR. The K66A mutation resulted in the lowest AHIII T cell, response and the lowest binding affinity, which suggests that the T cell, response may correlate with affinity. Importantly, the K66A mutation does, not affect the conformation of the peptide. The change in affinity appears, to be due to a loss in hydrogen bonds in the interface as a result of a, conformational change in the TCR complementarity-determining region 3, (CDR3) loop. Isothermal titration calorimetry confirmed the loss of, hydrogen bonding by a large loss in enthalpy. Our findings are, inconsistent with the notion that the CDR1 and CDR2 loops of the TCR are, responsible for MHC restriction, while the CDR3 loops interact solely with, the peptide. Instead, we present here an MHC mutation that does not change, the conformation of the peptide, yet results in an altered conformation of, a CDR3.

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

2JCC is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.

Reference

Single MHC Mutation Eliminates Enthalpy Associated with T Cell Receptor Binding., Miller PJ, Pazy Y, Conti B, Riddle D, Appella E, Collins EJ, J Mol Biol. 2007 Jul 26;. PMID:17825839

Page seeded by OCA on Mon Nov 12 22:54:10 2007