Bacterial chemotaxis is one of the best understood signaling systems in biology. It is one of a large number of """"""""two component"""""""" sensory systems in bacteria that use two proteins, a histidine auto kinase (CheA) and the response regulator proteins (CheY and CheB) that are the kinase substrates that are phosphorylated on aspartate residues. Phosphorylation of the response regulator domain modulates its interactions with its target domain(s) resulting in increased or decreased affinity for the other domain, depending on the system. We propose to use modern nuclear magnetic resonance techniques and other physical methods to answer questions in two specific aims: (1) What is the structural basis for the modulation of the kinase activity of CheA. CheA forms a hetero-trimeric complex with the transmembrane chemotaxis receptors and the coupling protein CheW. The receptors compare the current environment by binding attractant ligands to a memory of the recent past stored as methylation of certain glutamate resides in the receptors. How do the receptors make that comparison? How do they transmit that information to CheA to modulate its activity. (2) Phosphorylated CheY, produced by CheA, controls the sense of rotation of the bacterial rotary flagellar motors. The first step in the process is the binding to a recognition sequence in FliM, a protein of the """"""""switch complex """""""" made up of three proteins (FliM, FliG and FliN) located on the rotor of the motor. How does this binding event result in a change in the sense of rotation of the motor? How does the CheY-FliM complex communicate this information to the rest of the components of the motor?
Bacteria use rotary motors to swim toward beneficial chemicals and away from harmful ones. We are studying the biochemical reactions that allow them to decide where to swim and how to control their motors.
|Wang, Xiqing; Vallurupalli, Pramodh; Vu, Anh et al. (2014) The linker between the dimerization and catalytic domains of the CheA histidine kinase propagates changes in structure and dynamics that are important for enzymatic activity. Biochemistry 53:855-61|
|Ortega, Davi R; Mo, Guoya; Lee, Kwangwoon et al. (2013) Conformational coupling between receptor and kinase binding sites through a conserved salt bridge in a signaling complex scaffold protein. PLoS Comput Biol 9:e1003337|
|Wang, Xiqing; Wu, Chun; Vu, Anh et al. (2012) Computational and experimental analyses reveal the essential roles of interdomain linkers in the biological function of chemotaxis histidine kinase CheA. J Am Chem Soc 134:16107-10|
|Wang, Xiqing; Vu, Anh; Lee, Kwangwoon et al. (2012) CheA-receptor interaction sites in bacterial chemotaxis. J Mol Biol 422:282-90|
|Mo, Guoya; Zhou, Hongjun; Kawamura, Tetsuya et al. (2012) Solution structure of a complex of the histidine autokinase CheA with its substrate CheY. Biochemistry 51:3786-98|
|Levenson, Robert; Zhou, Hongjun; Dahlquist, Frederick W (2012) Structural insights into the interaction between the bacterial flagellar motor proteins FliF and FliG. Biochemistry 51:5052-60|
|Vu, Anh; Wang, Xiqing; Zhou, Hongjun et al. (2012) The receptor-CheW binding interface in bacterial chemotaxis. J Mol Biol 415:759-67|
|Vu, Anh; Hamel, Damon J; Zhou, Hongjun et al. (2011) The structure and dynamic properties of the complete histidine phosphotransfer domain of the chemotaxis specific histidine autokinase CheA from Thermotoga maritima. J Biomol NMR 51:49-55|
|Park, M-J; Dahlquist, F W; Doyle 3rd, F J (2007) Simultaneous high gain and wide dynamic range in a model of bacterial chemotaxis. IET Syst Biol 1:222-9|
|Dyer, Collin M; Dahlquist, Frederick W (2006) Switched or not?: the structure of unphosphorylated CheY bound to the N terminus of FliM. J Bacteriol 188:7354-63|
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