2hp4
From Proteopedia
Computational design and crystal structure of an enhanced affinity mutant human CD8-alpha-alpha co-receptor
Structural highlights
DiseaseCD8A_HUMAN Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:608957. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections. FunctionCD8A_HUMAN Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing. CD8 alpha chains binds to class I MHC molecules alpha-3 domains. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Boulter JM | Cole DK | Gao GF | Glick M | Jakobsen BK | Rizkallah PJ
