2WII

Complement C3b in complex with factor H domains 1-4

Summary for 2WII

• Entry DOI: 10.2210/pdb2wii/pdb
• Related: 1FHC 1HFH 1OJV 2A73 2A74 2G7I 2ICF 2JGW 2JGX 2RLP 2RLQ 2V8E 2W80 2W81
• Descriptor: COMPLEMENT C3 BETA CHAIN, COMPLEMENT C3B ALPHA' CHAIN, COMPLEMENT FACTOR H, ... (8 entities in total)
• Functional Keywords: immune system, sushi, secreted, polymorphism, glycoprotein, complement system, complement pathway, immune response, innate immunity, disease mutation, inflammatory response, complement alternate pathway, cleavage on pair of basic residues, age-related macular degeneration, regulator of complement activation, alternative pathway, alternative splicing, phosphoprotein, disulfide bond, thioester bond
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P01024 P01024
• Total number of polymer chains: 3
• Total formula weight: 209591.19

Authors

Wu, J.,Janssen, B.J.C.,Gros, P. (deposition date: 2009-05-12, release date: 2009-06-09, Last modification date: 2024-10-16)

Primary citation

Wu, J.,Wu, Y.Q.,Ricklin, D.,Janssen, B.J.,Lambris, J.D.,Gros, P.
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.
Nat. Immunol., 10:728-733, 2009

PubMed Abstract: Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insight into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target, complement fragment C3b. FH interacted with multiple domains of C3b, covering a large, extended surface area. The structure indicated that FH destabilizes the C3 convertase by competition and electrostatic repulsion and that FH enables proteolytic degradation of C3b by providing a binding platform for protease factor I while stabilizing the overall domain arrangement of C3b. Our results offer general models for complement regulation and provide structural explanations for disease-related mutations in the genes encoding both FH and C3b.

PubMed: 19503104
DOI: 10.1038/ni.1755

Experimental method

X-RAY DIFFRACTION (2.7 Å)