Professor, Molecular Biosciences
University of Kansas
NMR and Computational Studies of Protein Translocation in Bacterial Needles (2008-10)
Many Gram-negative bacteria inject virulence factors (effectors) into the host cell through a type III secretion system (TTSS) injectisome that is comprised of a basal body, a needle, and a tip. The external needle is formed by the assembly of approximately 120 copies of needle monomers around a central channel. However, the structures of the N-terminal regions of needle monomers that form the inner channel are not well defined due to their flexible nature. In this proposal, we will combine theoretical, computational, and experimental approaches to determine the structure of the N-terminal regions of the needle proteins, refine the needle model, and characterize the energetics of how proteins are transported across this channel.
Since the bacterial pathogens that use the TTSS injectisome pose major problems in public health and safety (due to the diverse diseases they cause ranging from shigellosis to plaque and the development of antibiotic resistance), a comprehensive understanding of the translocation mechanism used in TTSS will facilitate vaccine and drug developments against the diseases caused by these bacteria.