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- Title
Factor B structure provides insights into activation of the central protease of the complement system.
- Authors
Milder, Fin J.; Gomes, Lucio; Schouten, Arie; Janssen, Bert J. C.; Huizinga, Eric G.; Romijn, Roland A.; Hemrika, Wieger; Roos, Anja; Daha, Mohamed R.; Gros, Piet
- 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-Å 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.
- Subjects
GROWTH factors; SERINE proteinases; VON Willebrand factor; PEPTIDES; LIGAND binding (Biochemistry); PROTEOLYTIC enzyme genes; ALLOSTERIC regulation
- Publication
Nature Structural & Molecular Biology, 2007, Vol 14, Issue 3, p224
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb1210