2BZM

Solution structure of the primary host recognition region of complement factor H

2BZM の概要

• エントリーDOI: 10.2210/pdb2bzm/pdb
• 関連するPDBエントリー: 1FHC 1HAQ 1HCC 1HFH 1HFI 1KOV
• 分子名称: COMPLEMENT FACTOR H (1 entity in total)
• 機能のキーワード: immune system, factor h, complement, hus, heparin, polyanions, immune response, innate immunity, complement alternate pathway
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: P08603
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14773.79

構造登録者

Herbert, A.P.,Uhrin, D.,Lyon, M.,Pangburn, M.K.,Barlow, P.N. (登録日: 2005-08-18, 公開日: 2006-03-22, 最終更新日: 2024-11-20)

主引用文献

Herbert, A.P.,Uhrin, D.,Lyon, M.,Pangburn, M.K.,Barlow, P.N.
Disease-Associated Sequence Variations Congregate in a Polyanion Recognition Patch on Human Factor H Revealed in Three-Dimensional Structure.
J.Biol.Chem., 281:16512-, 2006

PubMed Abstract: Mutations and polymorphisms in the regulator of complement activation, factor H, have been linked to atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis, and age-related macular degeneration. Many aHUS patients carry mutations in the two C-terminal modules of factor H, which normally confer upon this abundant 155-kDa plasma glycoprotein its ability to selectively bind self-surfaces and prevent them from inappropriately triggering the complement cascade via the alternative pathway. In the current study, the three-dimensional solution structure of the C-terminal module pair of factor H has been determined. A binding site for a fully sulfated heparin-derived tetrasaccharide has been delineated using chemical shift mapping and the C3d/C3b-binding site inferred from sequence comparisons and computational docking. The resultant information allows assessment of the likely consequences of aHUS-associated amino acid substitutions in this critical region of factor H. It is striking that, excepting those likely to perturb the three-dimensional structure, aHUS-associated missense mutations congregate in the polyanion-binding site delineated in this study, thus potentially disrupting a vital mechanism for control of complement on self-surfaces in the microvasculature of the kidney. It is intriguing that a single nucleotide polymorphism predisposing to age-related macular degeneration occupies another region of factor H that harbors a polyanion-binding site.

PubMed: 16533809
DOI: 10.1074/JBC.M513611200

実験手法

SOLUTION NMR