BioProject

Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. More...

Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: stress response, dose response, gene knockout Overall design: 8 samples were analyzed. Each sample was dye-swapped (2 replicates per condition) and hybridized against a standard control. Less...