5FO8

Crystal Structure of Human Complement C3b in Complex with MCP (CCP1-4)

Summary for 5FO8

• Entry DOI: 10.2210/pdb5fo8/pdb
• Related: 5FO7 5FO9 5FOA 5FOB
• Descriptor: COMPLEMENT C3, MEMBRANE COFACTOR PROTEIN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: lipid binding, lipid bianding, complement system, immune system, plasma protein, cofa activity, regulators of complement activity
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P01024 P15529; Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane ; Single- pass type I membrane protein : P01024
• Total number of polymer chains: 3
• Total formula weight: 206928.07

Authors

Forneris, F.,Wu, J.,Xue, X.,Gros, P. (deposition date: 2015-11-18, release date: 2016-04-06, Last modification date: 2024-11-20)

Primary citation

Forneris, F.,Wu, J.,Xue, X.,Ricklin, D.,Lin, Z.,Sfyroera, G.,Tzekou, A.,Volokhina, E.,Granneman, J.C.,Hauhart, R.,Bertram, P.,Liszewski, M.K.,Atkinson, J.P.,Lambris, J.D.,Gros, P.
Regulators of Complement Activity Mediate Inhibitory Mechanisms Through a Common C3B-Binding Mode.
Embo J., 35:1133-, 2016

PubMed 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° 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.

PubMed: 27013439
DOI: 10.15252/EMBJ.201593673

Experimental method

X-RAY DIFFRACTION (2.4 Å)