Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.600776
Title: Elucidating the role of bacterial SLC26 transporters
Author: Karinou, Eleni
ISNI:       0000 0004 5352 166X
Awarding Body: University of Dundee
Current Institution: University of Dundee
Date of Award: 2014
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Abstract:
The Solute Carrier 26 (SLC26) and Sulphate transporter (SulP) family is a ubiquitous superfamily of transporter proteins conserved from bacteria to man. Proteins within the SLC26/SulP family exhibit a wide variety of functions, transporting anions ranging from halides to bicarbonate. The functional importance of this family is illustrated by the fact that several inherited human diseases are caused by mutations in SLC26 genes. Although these proteins are present in almost all bacteria their physiological function is still unknown. The overall aim of my project was to use a combination of genetic and biochemical approaches to investigate the substrate and physiological role of YchM, the SulP protein found in the bacterial model organism Escherichia coli. The work presented here has identified that YchM is an aerobic succinate transporter at acid pH, re-named as DauA (for Dicarboxylic Acid Uptake system A). Using in vivo transport assays I studied the apparent kinetics and substrate specificity of DauA. Competition assays showed that DauA apart from succinate can transport fumarate with no preference on the protonation state of the substrate. I identified a further regulatory role for DauA affecting DctA, the main succinate transporter. I showed that DauA and DctA interact physically via their transmembrane domain forming a regulatory unit. More candidate proteins interacting with DauA have been identified by mass spectrometry suggesting a role for DauA in the acid resistance mechanism. Finally, preliminary results on the regulation showed that DauA is produced constitutively regardless of pH or carbon source the cells are grown in. A growth-phase-dependent regulation was observed when cells were grown in glucose and reduction of DauA under anaerobic conditions might indicate a level of regulation. This is the first study reporting that a member of the SLC26/SulP family acts as a bifunctional protein with transport and regulatory activity in the C4-dicarboxylic acid metabolism.
Supervisor: Javelle, Arnaud Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.600776  DOI: Not available
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