Ultrastructures and interactions of complement factors H and I.
The human complement regulatory protein, factor H, was examined by high resolution transmission electron microscopy. Results of electron microscopy confirm hydrodynamic analysis and indicate that factor H is a monomer of M(r) approximately 155,000. Factor H is an extended flexible molecule with a contour length of 495 A and a cross-sectional diameter of 34 A. Most images of factor H indicate that its polypeptide chain typically folds back on itself with the result that the average length of a factor H molecule is about half its contour length. Only one end of factor H associates with C3b. When bound to C3b, factor H still shows considerable conformational flexibility. Factor I is a bilobal protein of 130 A in length, and its two globular parts have maximal diameters of 54 and 49 A. The results establish that factor I is a two domain protein where the smaller subunit is a protease and the larger one is involved with binding C3b. Factor I binds C3b with a one-to-one stoichiometry in an ionic strength-dependent fashion. In the absence of sodium chloride an affinity constant of 5.7 x 10(5) M-1 was determined for factor I interaction with C3b. Whereas the Scatchard plot of factor I binding to C3b in the absence of factor H is linear, in the presence of factor H a curvilinear graph is obtained. The strong binding sites on C3b for factor I have an affinity at least 15-fold higher in the presence of factor H than in its absence. The results of both electron microscopy and binding studies were combined to compose a scheme envisioning how factors H and I cooperate for the processing of C3b.
DiScipio
R G
RG
Department of Immunology IMM 18, Scripps Research Institute, La Jolla, CA 92037.
D001665:Binding Sites; D003179:Complement C3b / Q000378:metabolism; D017242:Complement Factor H / Q000502:physiology* / Q000648:ultrastructure*; D017244:Complement Factor I / Q000502:physiology* / Q000648:ultrastructure*; D006801:Humans; D008854:Microscopy, Electron
C493495:CFH protein, human; D003179:Complement C3b; D017242:Complement Factor H; D017244:Complement Factor I