. 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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Miller, Michael R; Miller, Kelly A; Bian, Jiang et al. (2016) Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility. Nat Microbiol 1:16134
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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

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