Cells must acquire a variety of transition metal ions until they achieve a highly conserved ensemble of metal concentrations known as the metallome.   While highly conserved over evolution, metallomes undergo temporal fluxes in pathogenesis, during cellular proliferation and at the earliest stage of development.   Metallomes are controlled by metalloregulatory proteins, which sense changes in metal availability and adjust gene expression accordingly. Structural and thermodynamic studies of these metal receptors are providing new insights into the coordination chemistry and allosteric mechanisms that give rise to extreme sensitivity (i.e., zinc changes in femtomolar range and copper in zeptomolar range).  Quantitative physical methods (STEM-EDS, ICP-MS, X-ray fluorescence microscopy and fluorescent metal-specific probes) reveal connections between fluxes in subcellular metals and key cellular decisions such as cell cycle entry and exit.  New examples where metal fluxes trigger physiological change will be described including those controlling the earliest stage of mammalian development and infectious disease.

Inorganic chemistry controlling cellular physiology and development

244th National Meeting (2012)

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