Mechanism of sodium-coupling in sodium-coupled transporters

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Membrane protein transporters are integral membrane proteins that enable small molecules such as nutrients, ions, neurotransmitters, and toxins to be transported across cellular membranes. They do this by alternately opening and closing the binding sites to one side or the other of the membranes. They can be divided into two major groups. Primary transporters use energy sources such as ATP whereas secondary transporters use ion gradients to facilitate transport.

Mhp1 is a secondary transporter that harnesses the sodium ion gradient to drive the uptake of molecules (substrates) into the cell. It is a member of a large superfamily of proteins that also include human neurotransmitter proteins. It was the first protein in this superfamily to be solved in multiple conformations showing how the protein structure changes to allow it to transport molecules across the membrane.

Previous studies have shown how the sodium ion and substrate bind to the protein and revealed the conformational changes that accompany binding. The object of this project is to understand how binding and release of these molecules in this family of transporters drives the conformational changes and how the binding of the sodium ion is coupled with the binding of the substrate.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1782611 Studentship BB/M01116X/1 03/10/2016 31/03/2021 Caitlin Hatton
 
Description Crystallised a novel LeuT superfamily member, currently in the process of obtaining functional data. This novel family member when compared to Mhp1 reveals the conserved features of the alternating access model of secondary access transporters and begins to elucidate the role of sodium ion binding and the how sodium ion binding droves the conformational changes to allow solute to move across the membrane.
Exploitation Route Increase current knowledge about proteins related to Mhp1 and begin to elucidate the specific and non-specific binding of substrate and the role of sodium in this family of proteins. This knowledge will contribute to the knowledge of related neurotransmitters.
Sectors Education,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Public Science event 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact About 70 members of the public came to a public science evening, in which our lab showcased some research and the methods used.
Year(s) Of Engagement Activity 2018