Activation of the complement system constitutes a powerful host-defense mechanism for combating infection, and as such contributes to inflammation as a normal immune reaction and in pathogenesis. Although substantial progress has been realized in understanding the general biochemistry and biology of this complex effector process, most of the molecular details of the individual components comprising the system are lacking. This project will focus on factor B, a key protein of the properdin pathway, to investigate its mechanism of action, regulation, and primary structure. Our laboratory has provided strong evidence that factor B is a novel type of serine protease. The research described in the present investigation will extend these studies on factor B to include the following objectives: 1) completion of the majority of its primary structure, 2) determine its substrate specificity, restriction, and inhibitory properties, 3) identify important sites within the zymogen which contribute to the recognition and activation by factor D, and 4) probe its molecular association and regulation by C3b. It is expected that the results of these investigations will provide insight into the control mechanisms governing the activity of the C3 convertase (C3bBb) and will enhance our understanding of the role of factor B in a number of rheumatological diseases.
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| Ramesh, N; Sugumaran, M; Mole, J E (1988) Purification and characterization of two trypsin inhibitors from the hemolymph of Manduca sexta larvae. J Biol Chem 263:11523-7 |
