Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.743340
Title: Structural and functional analysis of ZraP in Salmonella typhimurium
Author: Zalm, Maria
ISNI:       0000 0004 7227 5740
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2017
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Abstract:
The impact of Salmonella infections on global health is significant, and its treatment and prevention have proven to be a medical as well as a social-economical challenge. A major contributor to the pathogenicity of Salmonella is its ability to adapt to changing environments, and thrive despite exposure to environmental stresses. The Gram-negative cell envelope plays an important role in the natural resistance of Salmonella against various antimicrobial agents, providing a buffer that protects the Salmonella cytoplasm from immediate cellular stress. Periplasmic chaperones play a vital role in the biogenesis, maintenance and repair of the outer membrane. Although these chaperones are well studied in Escherichia coli, their functions are less well understood in other Gram-negative pathogens. This study investigates the involvement of Salmonella Typhimurium periplasmic proteins CpxP, FkpA, HtrA, PpiA/D, Skp, SurA, Spy, ZraP, and YncJ in the protection against a range of environmental stresses that challenge the cell envelope. The results obtained suggest that both Skp and SurA are of significant importance in the maintenance of the outer membrane, whereas the remaining chaperones appear to be involved in the protection against a narrower range of stresses. Furthermore, this study presents new insights into the protein structure of the zincresponsive, periplasmic chaperone ZraP. Data collected using X-ray crystallography analysis and small-angle X-ray scattering suggest that ZraP forms a globular protein of higher oligomeric state. The formation of higher oligomeric structures is not dependent on zinc interactions, nor does zinc affect the overall protein envelope. Although natural substrates of ZraP remain enigmatic, functional analysis of ZraP shows that protein interactions between ZraP and malate dehydrogenase or DNA gyrase may render these enzymes inactive. Suppression of enzymatic activity is reduced in ZraP constructs disrupted in the C-terminal 139HRGGAH144 region, whereas the presence of excess zinc boosts interactions between ZraP and these enzymes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.743340  DOI: Not available
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