2OFS

Crystal structure of human CD59

2OFS の概要

• エントリーDOI: 10.2210/pdb2ofs/pdb
• 分子名称: CD59 glycoprotein (2 entities in total)
• 機能のキーワード: complement inhibitor, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P13987
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8774.93

構造登録者

Davies, C. (登録日: 2007-01-04, 公開日: 2007-05-29, 最終更新日: 2024-10-30)

主引用文献

Huang, Y.,Fedarovich, A.,Tomlinson, S.,Davies, C.
Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex.
Acta Crystallogr.,Sect.D, 63:714-721, 2007

PubMed Abstract: Human CD59 is a small membrane-bound glycoprotein that functions as an inhibitor of the membrane-attack complex (MAC) of the complement system by binding the complement proteins C8 and C9. The crystal structure of a soluble construct of CD59 has been determined to 2.1 A resolution. When compared with previous models of CD59 determined using NMR, some interesting differences are noted, including the position of helix alpha1, which contributes to the binding surface for C8 and C9. Interestingly, the crystal structure superimposes more closely with an updated NMR model of CD59 that was produced using Monte Carlo minimization, including helix alpha1. Mapping of mutations associated with enhanced or lowered inhibitory function of CD59 show the binding region to be located in a crevice between alpha1 and a three-stranded beta-sheet, as has been identified previously. Residues in the core of this region are well ordered in the electron density, in part owing to a network of stabilizing covalent and noncovalent interactions, and manifest an interesting 'striped' distribution of hydrophobic and basic residues. Docking of the same peptide that was modeled previously into the NMR structure shows that Arg55, which has been postulated to exist in 'open' and 'closed' positions, is intermediate in position between these two and is well placed to contact the peptide. Further clues regarding how CD59 interacts with small peptides arise from the crystal packing of this structure, which shows that a symmetry-related loop comprising residues 20-24 occupies a spatially similar position to the modeled peptide. This higher resolution structure of CD59 will facilitate a more precise dissection of its interactions with C8 and C9 and thus increase the likelihood of designing enhanced CD59-based therapeutics.

PubMed: 17505110
DOI: 10.1107/S0907444907015557

実験手法

X-RAY DIFFRACTION (2.12 Å)