UNDERSTANDING THE CHROMOSOMAL SEGREGATION ORGANIZATION IN M TUBERCULOSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose to study the organization of segrosome, the cellular apparatus for chromosome trafficking in human pathogen Mycobacterium tuberculosis. Bacterial chromosome segregation process is coupled to DNA replication and is not well-understood. Two proteins (ParA and ParB) and a set of original-proximal DNA sequences (parS) form the segrosome machinery. ParA is a motor protein that drives this process. ParB forms a nucleo-protein complex with the parS DNA sequences. The ParB-parS complex probably serves to pair-up the two chromosomes at the beginning of the segregation process. Our aim is to elucidate the stoichiometry and the three-dimensional organization of ParB-parS complex for the segrosome of M. tuberculosis. X-ray solution scattering data (SAXS) obtained from SSRL will be combined with additional experimental data and homology modeling approach to build a model of the ParB-parS complex. This model will reveal how it pairs-up the two chromosomes prior to partition and cell division.