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Tsong Prize awarded to Taylor Colburn

Tsong Prize awarded to Taylor Colburn

Undergraduate student Taylor Colburn was awarded the 2017 Tsong Prize for Undergraduate Research in the Department of Physics at Arizona State University for his work on Simulating the conformational transitions of the transmembrane symporter Mhp1.

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Molecular mechanism of ligand recognition by the Mhp1 transporter

Molecular mechanism of ligand recognition by the Mhp1 transporter

The hydantoin transporter Mhp1 is a sodium?coupled secondary active transport protein of the nucleobase?cation?symport family and shares the widespread 5?helix inverted repeat transporter architecture. Our previous work showed Mhp1 functions according to the alternating access mechanism. In our new paper in EMBO J , we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site?directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands.

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The alternating access mechanism in Mhp1

The alternating access mechanism in Mhp1

Secondary transporters couple the free energy stored in an ionic gradient to the movement of solutes across the cell membrane. The coupling enables these transmembrane proteins to transport small molecules against their own concentration gradients. The transporters function by cycling between different conformational states in which access to the central binding site is switched from the extracellular solution to the intracellular compartment. Using experimental and computational approaches we could visualize for the first time how this process occurs for a secondary transporter.

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Transporters

Transporters

Transporter proteins are used by cells to “pump” molecules or ions into or out of the cell. They are present in all cells (digestive system, nervous system, blood, …) with important roles in metabolism. Secondary active transporters move their substrates against a electrochemical potential gradient and therefore couple uptake/excretion to an energetically favourable flow of sodium ions or protons into the cell.

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