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Exploring the contributions of scaffold domain residues on ligand interactions in the Na+ /succinate transporter, VcINDY

Leone, Nikita (2024) Exploring the contributions of scaffold domain residues on ligand interactions in the Na+ /succinate transporter, VcINDY. Master of Science by Research (MScRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.105679) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:105679)

Language: English

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Members of the divalent anion sodium symporter (DASS) family, known as the SLC13 transporter family in humans, are secondary active transporters responsible for translocating substrates against their concentration gradient using an electrochemical gradient. DASS transporters are essential for regulating metabolic homeostasis and provides a pathway for Krebs cycle intermediates to move into and out of living cells. Disruptions of these transporters affects energy balance and fat storage, resulting in metabolic diseases like obesity and type 2 diabetes. Using VcINDY from Vibrio cholerae, a homologue of NaCT, we have explored the effects of scaffold domain residues on ligand interactions. In this study, we employed a thermostability-based screen using differential scanning fluorimetry (DSF) assays to monitor the stability of single alanine substitutions in the presence of varying concentrations of C4 and C5-dicarboxylates. While most of the residues had minimal effects on ligand interactions according to our DSF assay data, this work revealed 2 residues that appear to play a role in the thermostability and transport activity of VcINDY. We have shown these 2 conserved residues specifically affect only some ligands and that imitating these residues reduces the maximum velocity of transport, likely impacting transport efficiency. This work has revealed new insight into the mechanism of DASS transporters which are targets for the treatment of metabolic diseases.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Mulligan, Christopher
DOI/Identification number: 10.22024/UniKent/01.02.105679
Additional information: The author of this thesis has requested that it be held under closed access. We are sorry but we will not be able to give you access or pass on any requests for access. 26/04/24.
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 22 Apr 2024 07:35 UTC
Last Modified: 24 May 2024 15:45 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Leone, Nikita.

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