Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp016108vd73j
 Title: Natural and De Novo Proteins in Transition Metal Binding and Toxicity Authors: Hoegler, Kenric Advisors: Hecht, Michael Contributors: Molecular Biology Department Keywords: de novoE. colievolutionmetalproteinresistance Subjects: Molecular biologyBiochemistry Issue Date: 2016 Publisher: Princeton, NJ : Princeton University Abstract: Life as we know it would not exist without transition metals. In living organisms, these metals are almost always associated with protein scaffolds, in protein-metal complexes called metalloproteins. Metalloproteins are ubiquitous in nature (i.e. present across all three domains of life) and play a multitude of highly conserved and vital roles in living things. Despite their essential roles, if not properly regulated, transition metals can also be toxic to all living things. My thesis research has been geared towards sorting out this almost paradoxical relationship. In the work presented here, I used synthetic biological tools to investigate the past, present, and future of biological transition metals, in order to gain a more intimate understanding of 1) how metalloproteins may have first emerged in biology, and 2) the strategies that nature uses to manage these powerful but potentially toxic entities. The first part of this work focused on studying the innate capacity of ‘unevolved proteins’ to bind transition metals. This involved probing a combinatorial library of de novo proteins for the ability to complex various metal cations. The findings presented here demonstrate the ability to bind transition metals is a common feature of ‘unevolved proteins’. The second and third parts of this work aimed to sort out the strategies that cells use to manage transition metal toxicity. This was done by identifying natural and de novo proteins that enabled E. coli to grow in otherwise lethal concentrations of various transition metal ions. I was able to identify a large assortment of natural proteins that enabled E. coli to grow in otherwise lethal concentrations of cadmium, cobalt, copper, nickel, silver, and zinc; and one de novo protein that allowed E. coli to grow in otherwise lethal concentrations of copper. URI: http://arks.princeton.edu/ark:/88435/dsp016108vd73j Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu Type of Material: Academic dissertations (Ph.D.) Language: en Appears in Collections: Molecular Biology

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