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.
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.
Organisations
People |
ORCID iD |
Alexander Cameron (Primary Supervisor) | |
Caitlin Hatton (Student) |
Publications
Hall SCL
(2021)
Surface-tethered planar membranes containing the ß-barrel assembly machinery: a platform for investigating bacterial outer membrane protein folding.
in Biophysical journal
Hughes GW
(2019)
Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system.
in Nature microbiology
Hatton CE
(2022)
Structure of cytosine transport protein CodB provides insight into nucleobase-cation symporter 1 mechanism.
in The EMBO journal
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M01116X/1 | 30/09/2015 | 31/03/2024 | |||
1782611 | Studentship | BB/M01116X/1 | 02/10/2016 | 30/03/2021 | 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 |