Access Type

Open Access Thesis

Date of Award

January 2023

Degree Type

Thesis

Degree Name

M.S.

Department

Biochemistry and Molecular Biology

First Advisor

Bharati Mitra

Abstract

The disfunction or misregulation of the ZIP family of metal ion transporters has been linked to a plethora of diseases and cancers in humans. Zn2+ is the primary substrate for ZIPs and is transported through the M1 metal binding site, though this activity is stimulated through the binding of Fe2+ in the M2 metal binding site. The members of ZIP Subfamily II are predicted to have an inactive M2 site due to the lack of Fe2+ transport and from a previously generated homology model. This work utilizes homology modelling, whole cell metal ion uptake assays, and growth studies in minimal media to analyze the impact of Subfamily II-like M2 mutations on the Zn2+ and Fe2+ transport of ZupT, the ZIP native to Escherichia coli which has an active M2 site. These mutations severely inhibit ZupT’s Fe2+ transport while Zn2+ transport is relatively unaltered, providing further evidence that the members of ZIP Subfamily II have an inactive M2 site. The regulation of ZIPs remains mostly unknown, so identifying an inactive regulatory site in Subfamily II demonstrates that ZIPs are diverse and may require diverse treatments for ZIP-related diseases.

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