SMALL ANGLE X-RAY SCATTERING STUDIES OF THE DISAGGREGASE HSP104

Illinois Institute Of Technology, Chicago IL

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Abstract

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 sought to compare the low resolution solution structures of conventional histone complexes and their counterpart at the centromere, the region of the chromosome that directs its own inheritance. Our hypothesis going into these studies was that structural alteration in the centromeric histone 'variant', CENP-A, are important for epigenetically marking the centromere locus. Previous findings had indicated that the location of mammalian centromeres is not specified by a particular DNA sequence and there is strong evidence that there is a strong epigenetic component to specifying centromere location. Our SAXS experiments are key to our efforts to define the physical basis for the epigenetic centromere 'mark'. We found that the centromere version of the complex is more compact than the conventional complex by ~10 angstroms. This was in general agreement with our findings from crystal structures of the same proteins. This work was a critical component of the study that was just published in Nature.