Abstract

By combined use of immunochemistry, lipid model membranes, and biophysical techniques such as membrane probe spectroscopy (EPR and fluorescence), black-lipid membranes, and lipid monolayer techniques, it is proposed to investigate the molecular events that occur during complement mediated membranolysis. The function of the membrane attack complex (MAC) of complement will be investigated with respect to penetration into membranes, formation of a protein-walled channel across the membrane, reorientation of ordered bilayer lipids, and interaction with other membrane proteins. The virolytic action of MAC proteins will be studied in particular. A fuller understanding of the role of complement in the body's immune defense system will undoubetedly open the way to new and better means of controlling infections, allergic disorders, and autoimmune diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019478-05
Application #
3128822
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1982-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
Schools of Veterinary Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Wang, Y; Bjes, E S; Esser, A F (2000) Molecular aspects of complement-mediated bacterial killing. Periplasmic conversion of C9 from a protoxin to a toxin. J Biol Chem 275:4687-92
Thielens, N M; Enrie, K; Lacroix, M et al. (1999) The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s. J Biol Chem 274:9149-59
Rossi, V; Bally, I; Thielens, N M et al. (1998) Baculovirus-mediated expression of truncated modular fragments from the catalytic region of human complement serine protease C1s. Evidence for the involvement of both complement control protein modules in the recognition of the C4 protein substrate. J Biol Chem 273:1232-9
Esser, A F; Tarnuzzer, R W; Tomlinson, S et al. (1996) Horse complement protein C9: primary structure and cytotoxic activity. Mol Immunol 33:725-33
Tomlinson, S; Wang, Y; Ueda, E et al. (1995) Chimeric horse/human recombinant C9 proteins identify the amino acid sequence in horse C9 responsible for restriction of hemolysis. J Immunol 155:436-44
Esser, A F (1994) The membrane attack complex of complement. Assembly, structure and cytotoxic activity. Toxicology 87:229-47
Esser, A F; Thielens, N M; Zaccai, G (1993) Small angle neutron scattering studies of C8 and C9 and their interactions in solution. Biophys J 64:743-8
Tomlinson, S; Ueda, E; Maruniak, J E et al. (1993) The expression of hemolytically active human complement protein C9 in mammalian, insect, and yeast cells. Protein Expr Purif 4:141-8
Tomlinson, S; Stanley, K K; Esser, A F (1993) Domain structure, functional activity, and polymerization of trout complement protein C9. Dev Comp Immunol 17:67-76
Tomlinson, S; Esser, A F (1992) Rapid immunological screening for protein expression in yeast transformants. Biotechniques 13:710-1

Showing the most recent 10 out of 27 publications