5FOA: Crystal Structure Of Human Complement C3b In Complex With Daf (ccp2-4)

Citation:
Abstract
Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i-iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b-binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100 degrees rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease-related mutations and immune evasion.
PDB ID: 5FOADownload
MMDB ID: 138149
PDB Deposition Date: 2015/11/18
Updated in MMDB: 2016/06
Experimental Method:
x-ray diffraction
Resolution: 4.19  Å
Source Organism:
Similar Structures:
Biological Unit for 5FOA: trimeric; determined by software (PQS)
Molecular Components in 5FOA
Label Count Molecule
Proteins (3 molecules)
1
Complement C3 Beta Chain(Gene symbol: C3)
Molecule annotation
1
Complement C3B Alpha Chain(Gene symbol: C3)
Molecule annotation
1
Decay Accelerating Factor, Cd55(Gene symbol: CD55)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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