PMID: 17310251

 

    Legend: Sugar

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

Abstract :
  1. Factor B is the central protease of the complement system of immune defense
  2. 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
  3. The canonical activation helix of the Von Willebrand factor A (VWA) domain is displaced by a helix from the preceding domain linker
  4. The two helices conformationally link the scissile-activation peptide and the metal ion-dependent adhesion site required for binding of the ligand C3b
  5. The data suggest that C3b binding displaces the three N-terminal control domains and reshuffles the two central helices
  6. 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
  7. This allosteric mechanism is crucial for tight regulation of the complement-amplification step in the immune response