The serum complement system represents a group of proteins which upon activation elaborate biologically active fragments participating in host defense against pathogens and in the pathogenesis of human hypersensitivity diseases, exemplified by rheumatoid arthritis and systemic lupus erythematosus. Clearly, the central event in the generation of the biological activities of complement is the cleavage of a single Arg-Ser bond near the NH2-terminus of the Alpha chain of C3. The long-term objective of this project is to contribute to current understanding of the formation, regulation, and mechanism of action of the two intrinsic complement enzymes, termed C3-convertase, which catalyze this cleavage. To accomplish this goal we propose to continue collecting detailed information at the molecular level on the proteins participating in the assembly of these key complement enzymes. The main emphasis will be on the biology and regulation of D and the structure of C2.
The specific aims i nclude: 1) Studies on the in-vitro biosynthesis of D by cultured human peripheral blood monocytes/macrophages as well as monocyte and hepatoma cell lines. The primary objective of these studies will be to identify and characterize an intracellular precursor of D however, other important aspects of D biosynthesis will also be investigated. 2) Studies on the three-dimensional structure of D and on the structural determinants of its restricted catalytic activity. Monoclonal antibodies and antibodies of predetermined specificity will be used to accomplish this goal. 3) Investigations on the identity, physicohemical properties and possible functional effects of a putative serum inhibitor of D. 4) Structural analysis of C2 and its main fragments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021067-04
Application #
3130986
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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