3ZD1

STRUCTURE OF THE TWO C-TERMINAL DOMAINS OF COMPLEMENT FACTOR H RELATED PROTEIN 2

Summary for 3ZD1

• Entry DOI: 10.2210/pdb3zd1/pdb
• Related: 3ZD2
• Descriptor: COMPLEMENT FACTOR H-RELATED PROTEIN 2, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: immune system, cfhr-2, cfhr2, fhr2
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P36980
• Total number of polymer chains: 2
• Total formula weight: 29227.14

Authors

Caesar, J.J.E.,Goicoechea de Jorge, E.,Pickering, M.C.,Lea, S.M. (deposition date: 2012-11-23, release date: 2013-03-13, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)