Bacterial chemotaxis, perhaps the most primitive behavioral system in biology, is nonetheless quite complex. Much has been learned about the structure of the motor organelle, the flagellum, in terms of its structural genes and its components. The sequences of essentially all of the flagellar genes are known. This proposal focuses on the process of flagellar assembly and on the attendant process of export of external components. The goal is to establish the components of the export apparatus (as opposed to the proteins exported), where the apparatus is located, and ultimately how it functions. Several candidates for export apparatus components exist, based on a miscellany of information deriving from previous studies. Basic information will be gathered as to the general cellular location and stoichiometry of putative components of the apparatus; evidence for interactions among them will be sought by intergenic suppression and affinity techniques. Several specific questions regarding process will be addressed, such as how the lengths of substructures like the flagellar hook are controlled, and whether there are scaffolding elements that are present during assembly and then discarded. How a cell assembles a complex organelle is a fundamental question, and the bacterial flagellum is an excellent system for its exploration. Thus the proposed research is of intrinsic biological interest and importance. Further significance derives from the recent realization that export of flagellar proteins and export of virulence factors by pathogenic bacteria like Yersinia pestis are somehow related. There are at least four putative export components of the two systems that are remarkably similar (up to 50% amino acid identity), a finding that is likely to have significant mechanistic and evolutionary implications. An understanding of how a pathogen exports molecules like invasins and adhesins could aid in designing clinical approaches for combating pathogens. Study of both systems is likely to be mutually beneficial in terms of understanding this special class of export process; the fact that the flagellar genetic system is better understood may enable it to provide a leading role in the investigation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012202-25
Application #
2653788
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1977-01-01
Project End
1999-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
25
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Ferris, Hedda U; Minamino, Tohru (2006) Flipping the switch: bringing order to flagellar assembly. Trends Microbiol 14:519-26
McMurry, Jonathan L; Murphy, James W; Gonzalez-Pedrajo, Bertha (2006) The FliN-FliH interaction mediates localization of flagellar export ATPase FliI to the C ring complex. Biochemistry 45:11790-8
Minamino, Tohru; Imada, Katsumi; Tahara, Aiko et al. (2006) Crystallization and preliminary X-ray analysis of Salmonella FliI, the ATPase component of the type III flagellar protein-export apparatus. Acta Crystallogr Sect F Struct Biol Cryst Commun 62:973-5
Minamino, Tohru; Ferris, Hedda U; Moriya, Nao et al. (2006) Two parts of the T3S4 domain of the hook-length control protein FliK are essential for the substrate specificity switching of the flagellar type III export apparatus. J Mol Biol 362:1148-58
Gonzalez-Pedrajo, Bertha; Minamino, Tohru; Kihara, May et al. (2006) Interactions between C ring proteins and export apparatus components: a possible mechanism for facilitating type III protein export. Mol Microbiol 60:984-98
Moriya, Nao; Minamino, Tohru; Hughes, Kelly T et al. (2006) The type III flagellar export specificity switch is dependent on FliK ruler and a molecular clock. J Mol Biol 359:466-77
Minamino, Tohru; Kazetani, Ken-ichi; Tahara, Aiko et al. (2006) Oligomerization of the bacterial flagellar ATPase FliI is controlled by its extreme N-terminal region. J Mol Biol 360:510-9
Ferris, Hedda U; Furukawa, Yukio; Minamino, Tohru et al. (2005) FlhB regulates ordered export of flagellar components via autocleavage mechanism. J Biol Chem 280:41236-42
Kariuki, T M; Farah, I O (2005) Resistance to re-infection after exposure to normal and attenuated schistosome parasites in the baboon model. Parasite Immunol 27:281-8
Saijo-Hamano, Yumiko; Imada, Katsumi; Minamino, Tohru et al. (2005) Crystallization and preliminary X-ray analysis of the C-terminal cytoplasmic domain of FlhA, a membrane-protein subunit of the bacterial flagellar type III protein-export apparatus. Acta Crystallogr Sect F Struct Biol Cryst Commun 61:599-602

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