. Many species of bacteria swim by means of flagella, helical filaments that function as propellers attached to rotary motors in the cell membrane. The flagellar motor is fueled by the membrane ion gradient and is capable of rapid rotation in either the clockwise or counterclockwise direction. By controlling reversals in motor direction, cells can direct their movement toward conditions that favor survival and growth. The structure and molecular mechanism of the flagellum is not understood in detail, but proteins with key roles in rotation and clockwise/counterclockwise switching have been identified. Rotation involves a stator (non-rotating part) formed from the membrane proteins MotA and MotB, and a rotor formed from FliG, FliM, and FliN. Recently, crystallography has been used in combination with biochemical methods to generate a model for the overall arrangement of proteins on the rotor. In the work proposed here, this structural model of the flagellar rotor will be developed further using a variety of biochemical, mutational, and structural approaches, and the new structural information will be utilized to address the molecular mechanisms of flagellar rotation, switching, and assembly. The long-term goal of this work is to understand the structure, assembly, and mechanism of the bacterial flagellar motor. Relevance. Flagellar motility is a factor in the virulence of many human pathogens, including those that cause ulcers, syphilis, urinary tract infections;burn wound infections, and some diarrhea. Furthermore, central structures in the flagellum are structurally and mechanistically related to the protein secretion apparatus (termed the type-Ill secretion system) that many pathogenic bacteria use to inject virulence factors into the cells they infect. In addition to its direct relevance for bacterial pathogenesis, the knowledge gained will have implications for the broader biological questions of cellular motility, organelle assembly, and membrane transport.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Prokaryotic Cell and Molecular Biology Study Section (PCMB)
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Gindhart, Joseph G
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University of Utah
Schools of Arts and Sciences
Salt Lake City
United States
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Sircar, Ria; Greenswag, Anna R; Bilwes, Alexandrine M et al. (2013) Structure and activity of the flagellar rotor protein FliY: a member of the CheC phosphatase family. J Biol Chem 288:13493-502
Paul, Koushik; Carlquist, William C; Blair, David F (2011) Adjusting the spokes of the flagellar motor with the DNA-binding protein H-NS. J Bacteriol 193:5914-22
Paul, Koushik; Gonzalez-Bonet, Gabriela; Bilwes, Alexandrine M et al. (2011) Architecture of the flagellar rotor. EMBO J 30:2962-71
Paul, Koushik; Brunstetter, Duncan; Titen, Sienna et al. (2011) A molecular mechanism of direction switching in the flagellar motor of Escherichia coli. Proc Natl Acad Sci U S A 108:17171-6
Sarkar, Mayukh K; Paul, Koushik; Blair, David F (2010) Subunit organization and reversal-associated movements in the flagellar switch of Escherichia coli. J Biol Chem 285:675-84
Paul, Koushik; Nieto, Vincent; Carlquist, William C et al. (2010) The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism. Mol Cell 38:128-39
Sarkar, Mayukh K; Paul, Koushik; Blair, David (2010) Chemotaxis signaling protein CheY binds to the rotor protein FliN to control the direction of flagellar rotation in Escherichia coli. Proc Natl Acad Sci U S A 107:9370-5
Kim, Eun A; Price-Carter, Marian; Carlquist, William C et al. (2008) Membrane segment organization in the stator complex of the flagellar motor: implications for proton flow and proton-induced conformational change. Biochemistry 47:11332-9
Paul, Koushik; Harmon, Jacob G; Blair, David F (2006) Mutational analysis of the flagellar rotor protein FliN: identification of surfaces important for flagellar assembly and switching. J Bacteriol 188:5240-8
Yakushi, Toshiharu; Yang, Junghoon; Fukuoka, Hajime et al. (2006) Roles of charged residues of rotor and stator in flagellar rotation: comparative study using H+-driven and Na+-driven motors in Escherichia coli. J Bacteriol 188:1466-72

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