Coexistence of closed and open conformations of complement factor B in the alternative pathway C3bB(Mg2+) proconvertase.
Complement factor B (fB) circulates in plasma as a proenzyme that, upon binding to C3b in the presence of Mg(2+), is cleaved by factor D to produce Ba and Bb fragments. Activated Bb remains bound to C3b organizing the alternative pathway C3 convertase (C3bBb). Recently, we have visualized the stable C3bB(Ni(2+)) proconvertase using electron microscopy, revealing a large conformational change of the C3b-bound fB likely exposing the fD-cleavage site. In contrast, the crystal structure of the proconvertase formed by human fB and the cobra venom factor reveals fB in the closed conformation of the proenzyme. In this study, we have used single-particle electron microscopy and image processing to examine the C3bB(Mg(2+)) proconvertase. We describe two C3bB(Mg(2+)) conformations, one resembling cobra venom factor, likely representing the loading state of fB to C3b, and another identical with C3bB(Ni(2+)). These data illustrate the coexistence of C3b-bound fB in closed and open conformations that either exist in equilibrium or represent structural transitions during the assembly of the C3bB proconvertase.
Torreira
Eva
E
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Instituto Reina Sofía de Investigaciones Nefrológicas. Ramiro de Maeztu 9, Madrid, Spain.
Tortajada
Agustín
A
Montes
Tamara
T
Rodríguez de Córdoba
Santiago
S
Llorca
Oscar
O
D051561:Complement C3 Convertase, Alternative Pathway / Q000737:chemistry*; D003179:Complement C3b / Q000737:chemistry*; D011415:Complement Factor B / Q000737:chemistry*; D003170:Complement Pathway, Alternative; D004546:Elapid Venoms / Q000737:chemistry; D006801:Humans; D021621:Imaging, Three-Dimensional; D008274:Magnesium / Q000737:chemistry; D008854:Microscopy, Electron; D020836:Protein Structure, Quaternary
D004546:Elapid Venoms; C016310:cobra venom factor; D003179:Complement C3b; D051561:Complement C3 Convertase, Alternative Pathway; D011415:Complement Factor B; D008274:Magnesium