SAXS INVESTIGATION OF ALLOSTERY IN NICKEL-RESPONSIVE TRANSCRIPTIONAL REGULATION

Stanford University, Stanford CA

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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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent XAS studies of nickel-dependent transcriptional regulators NikR and RcnR in the PI's research labs show that, while many metals are bound with high affinity, the ligands used to bind different metals are distinct and result in metal sites with different coordination numbers and geometries. In vivo, the transcriptional regulators were shown respond only to specific metals. One possible explanation is that the metal bound to the protein favors specific conformations of the protein, and only those with the cognate metal bound are biologically active. We plan to examine two or more different metal complexes (e.g., Ni(II)- and Co(II)-NikR) for direct experimental evidence of this metal-specific allosteric mechanism. If we are able to detect a significant conformational change, we will propose to study the full set of metals for NikR (a nickel-repsonsive transcriptional repressor) and RcnR (a nickel- and cobalt-responsive de-repressor).