Title : Factor B structure provides insights into activation of the central
protease of the complement system
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