In some pathogens, directed motility towards external chemicals (chemotaxis) is crucial for colonization and infection. Signal transduction systems that mediate such responses are potential targets for antimicrobial drug development. A key molecular event during chemotaxis is the interaction between the phosphorylated response regulator CheY (CheY-P) and the flagellar switch complex. This recognition event results in switching the direction of flagellar rotation. Whether the flagella rotate clockwise or counterclockwise determine if the bacteria will tumble or swim smoothly. Controlling the frequency of switching moves the bacteria towards a more favorable environment. CheY-P targets the switch protein FliM in the flagellar motor. The structure of the central domain of FliM reveals homology to a family of CheY-phosphatases which include CheC and CheX. Thus, the same structural motif binds CheY-P for both signal termination and signal output.
I aim to understand how CheY is recognized by the phosphatases CheC and CheX during signal termination by determining crystal structures of CheX (and/or CheC) bound to CheY-P, or stabilize analogs thereof. In parallel to understand the mechanism of flagellar switching and its relationship to signal termination I aim to determine the crystal structure of FliM: CheY-P and other key elements of the flagellar switch complex.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
3F31GM078789-03S1
Application #
7870947
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Gaillard, Shawn R
Project Start
2006-08-16
Project End
2009-12-15
Budget Start
2008-08-16
Budget End
2009-12-15
Support Year
3
Fiscal Year
2009
Total Cost
$19,187
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Paul, Koushik; Gonzalez-Bonet, Gabriela; Bilwes, Alexandrine M et al. (2011) Architecture of the flagellar rotor. EMBO J 30:2962-71