3ZD2

THE STRUCTURE OF THE TWO N-TERMINAL DOMAINS OF COMPLEMENT FACTOR H RELATED PROTEIN 1 SHOWS FORMATION OF A NOVEL DIMERISATION INTERFACE

3ZD2 の概要

• エントリーDOI: 10.2210/pdb3zd2/pdb
• 関連するPDBエントリー: 3ZD1
• 分子名称: COMPLEMENT FACTOR H-RELATED PROTEIN 1, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: immune system, cfhr-1, cfhr1, fhr1
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: Q03591
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29791.04

構造登録者

Caesar, J.J.E.,Goicoechea de Jorge, E.,Pickering, M.C.,Lea, S.M. (登録日: 2012-11-23, 公開日: 2013-03-13, 最終更新日: 2024-11-06)

主引用文献

Goicoechea De Jorge, E.,Caesar, J.J.E.,Malik, T.H.,Patel, M.,Colledge, M.,Johnson, S.,Hakobyan, S.,Morgan, B.P.,Harris, C.L.,Pickering, M.C.,Lea, S.M.
Dimerization of Complement Factor H-Related Proteins Modulates Complement Activation in Vivo.
Proc.Natl.Acad.Sci.USA, 110:4685-, 2013

PubMed Abstract: The complement system is a key component regulation influences susceptibility to age-related macular degeneration, meningitis, and kidney disease. Variation includes genomic rearrangements within the complement factor H-related (CFHR) locus. Elucidating the mechanism underlying these associations has been hindered by the lack of understanding of the biological role of CFHR proteins. Here we present unique structural data demonstrating that three of the CFHR proteins contain a shared dimerization motif and that this hitherto unrecognized structural property enables formation of both homodimers and heterodimers. Dimerization confers avidity for tissue-bound complement fragments and enables these proteins to efficiently compete with the physiological complement inhibitor, complement factor H (CFH), for ligand binding. Our data demonstrate that these CFHR proteins function as competitive antagonists of CFH to modulate complement activation in vivo and explain why variation in the CFHRs predisposes to disease.

PubMed: 23487775
DOI: 10.1073/PNAS.1219260110

実験手法

X-RAY DIFFRACTION (1.99 Å)