2OK5

Human Complement factor B

Summary for 2OK5

• Entry DOI: 10.2210/pdb2ok5/pdb
• Related: 2I6Q
• Descriptor: Complement factor B, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: pro-enzyme, serine protease domain, von willebrand factor-a domain, ccp domain, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00751
• Total number of polymer chains: 1
• Total formula weight: 87739.27

Authors

Milder, F.J.,Gomes, L.,Schouten, A.,Janssen, B.J.C.,Huizinga, E.G.,Romijn, R.A.,Hemrika, W.,Roos, A.,Daha, M.R.,Gros, P. (deposition date: 2007-01-16, release date: 2007-02-27, Last modification date: 2024-11-20)

Primary citation

Milder, F.J.,Gomes, L.,Schouten, A.,Janssen, B.J.,Huizinga, E.G.,Romijn, R.A.,Hemrika, W.,Roos, A.,Daha, M.R.,Gros, P.
Factor B structure provides insights into activation of the central protease of the complement system.
Nat.Struct.Mol.Biol., 14:224-228, 2007

PubMed Abstract: Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domain is displaced by a helix from the preceding domain linker. The two helices conformationally link the scissile-activation peptide and the metal ion-dependent adhesion site required for binding of the ligand C3b. The data suggest that C3b binding displaces the three N-terminal control domains and reshuffles the two central helices. Reshuffling of the helices releases the scissile bond for final proteolytic activation and generates a new interface between the VWA domain and the serine protease domain. This allosteric mechanism is crucial for tight regulation of the complement-amplification step in the immune response.

PubMed: 17310251
DOI: 10.1038/nsmb1210

Experimental method

X-RAY DIFFRACTION (2.3 Å)