The long-term goal is to understand mechanisms for the pathogenic action of channel-forming bacterial toxins. Work focuses on the Staphylococcal toxins a-hemolysin, g-hemolysin and leukocidin. These toxins assemble from soluble monomers to inserted transmembrane oligomers that kill several cell types, including human erythrocytes and leukocytes. The crystal structure of fully assembled a-hemolysin has been determined to a resolution of 1.9 A in the current funding period. Crystal structures of intermediates on the assembly pathway will now be determined to elucidate the mechanisms of assembly in molecular detail. Specific structures to be determined include water-soluble and membrane-bound forms of toxin protomers, oligomers complexed with phospholipids, individual components and assembled forms of g-hemolysin and leukocidin toxins, and site-directed mutants of a-hemolysin. The kinetics of assembly under conditions similar to those under which the toxins were crystallized will be determined for the purpose of structure/function correlation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051987-08
Application #
6519616
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Flicker, Paula F
Project Start
1995-01-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2004-06-30
Support Year
8
Fiscal Year
2002
Total Cost
$162,412
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032