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. Accurate chromosome segregation is required for propagation of all cells. Errors in this process are implicated in oncogenesis, developmental errors, and cell death. Crucial to proper partitioning of the chromosomes during cell division is the accurate duplication, assembly and regulation of the centrosome, which is responsible for forming the complex protein structure that segregates the genetic material. The spindle pole body (SPB) in yeast is the best characterized centrosome. Understanding its structure and assembly will provide important insights into the essential process of distributing the chromosomes in each cell division. The Sali lab developed the IMP software package to construct detailed models of the architecture of large macromolecular protein complexes. We propose to use IMP in an iterative process to construct a high resolution model of the central core of the yeast SPB. The distance constraints for the construction of the model will rely on currently available data and data generated by FRET and cross-linking analysis.
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