2hp4

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spinqualitylabelsall models PDB ID 2hp4 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.10Å
Ligands:	and
Coordinates:	save as pdb, mmCIF, xml

Computational design and crystal structure of an enhanced affinity mutant human CD8-alpha-alpha co-receptor

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Human CD8 is a T cell coreceptor, which binds to pHLA I and plays a pivotal role in the activation of cytotoxic T lymphocytes. Soluble recombinant CD8 alphaalpha has been shown to antagonize T cell activation, both in vitro and in vivo. However, because of a very low affinity for pHLA I, high concentrations of soluble CD8 alphaalpha are required for efficient inhibition. Based upon our knowledge of the wild-type CD8/pHLA I structure, we have designed and produced a mutated form of soluble CD8 alphaalpha that binds to pHLA I with approximately fourfold higher affinity. We have characterized the binding of the high affinity CD8 mutant using surface plasmon resonance and determined its structure at 2.1 A resolution using X-ray crystallography. The analysis of this structure suggests that the higher affinity is achieved by providing a larger side chain that allows for an optimal contact to be made between the HLA alpha3 loop and the mutated CDR-like loops of CD8.

Disease

Known disease associated with this structure: Megakaryoblastic leukemia, acute OMIM:[606078]

About this Structure

2HP4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Computational design and crystal structure of an enhanced affinity mutant human CD8 alphaalpha coreceptor., Cole DK, Rizkallah PJ, Boulter JM, Sami M, Vuidepot AL, Glick M, Gao F, Bell JI, Jakobsen BK, Gao GF, Proteins. 2007 Apr 1;67(1):65-74. PMID:17243170

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