Computational design and crystal structure of an enhanced affinity mutant human CD8 alphaalpha coreceptor.
Proteins
; 67(1): 65-74, 2007 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-17243170
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos CD8
Idioma:
En
Revista:
Proteins
Asunto de la revista:
BIOQUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Reino Unido