3ZD2: The Structure of the Two N-terminal Domains of Complement Factor H Related Protein 1 Shows Formation of a Novel Dimerisation Interface

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.
PDB ID: 3ZD2Download
MMDB ID: 108252
PDB Deposition Date: 2012/11/23
Updated in MMDB: 2013/04
Experimental Method:
x-ray diffraction
Resolution: 1.99  Å
Source Organism:
Similar Structures:
Biological Unit for 3ZD2: dimeric; determined by author and by software (PISA)
Molecular Components in 3ZD2
Label Count Molecule
Proteins (2 molecules)
Complement Factor H-related Protein 1(Gene symbol: CFHR1)
Molecule annotation
Chemicals (16 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB