Structural and functional analysis of SilP, a P1-type ATPase from the sil family involved in bacterial silver resistance.

Lead Research Organisation: University of Nottingham
Department Name: Sch of Biosciences

Abstract

Silver (Ag+) is a heavy metal commonly used within burns wards as a lining in bandages and as an additive within creams to help prevent infections, owing to heavy metals being highly toxic to bacterial cells. Due to the use of silver as a preventative treatment, certain strains of bacteria have developed resistance to silver. Analysis of the resistant bacteria identified the presence of a plasmid containing nine genes encoding for proteins believed to be involved in silver exportation, they were labelled sil proteins.
My current research focuses on one of these proteins, SilP, this is a P1B-type ATPase that exports Ag+ from the cytoplasm of the bacterial into the periplasm of the cell membrane at the expense of ATP. SilP follows the Post-Albers catalytic cycle, wherein there are four main conformational states of the protein during exportation of Ag+.
The main aim of my research looks at obtaining an overall structure of SilP, using both crystallography, Cryo-EM and neutron scattering. In addition to the overall structure is the aim of getting a structure at each of the four stages of the catalytic cycle, this would give an indication of metal movement within the protein and how it exports Ag+. Although the main aim is the structural determination of SilP, the other aims are to carry out functional assays looking at ATP usage and rate of Ag+ exportation as well as other biophysical aspects of SilP.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M008770/1 01/10/2015 30/09/2023
1944724 Studentship BB/M008770/1 01/10/2017 30/09/2021 Ryan Lithgo