2HP4

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

2HP4 の概要

• エントリーDOI: 10.2210/pdb2hp4/pdb
• 分子名称: T-cell surface glycoprotein CD8 alpha chain, SULFATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cd8, co-receptor, soluble protein, kd, protein engineering, immunotherapy, immune-suppressor, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P01732
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26537.72

構造登録者

Rizkallah, P.J.,Cole, D.K.,Jakobsen, B.K.,Boulter, J.M.,Glick, M.,Gao, G.F. (登録日: 2006-07-17, 公開日: 2007-02-06, 最終更新日: 2024-12-25)

主引用文献

Cole, D.K.,Rizkallah, P.J.,Boulter, J.M.,Sami, M.,Vuidepot, A.-L.,Glick, M.,Gao, F.,Bell, J.I.,Jakobsen, B.K.,Gao, G.F.
Computational design and crystal structure of an enhanced affinity mutant human CD8 alphaalpha coreceptor
Proteins, 67:65-74, 2007

PubMed 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.

PubMed: 17243170
DOI: 10.1002/prot.21176

実験手法

X-RAY DIFFRACTION (2.1 Å)