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AE1 Transport Modulation

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Anion Exchanger 1 (AE1) is the most abundant membrane protein in human red blood cells and the fastest known transporter. It plays a central role in facilitating carbon dioxide transport from tissues to the lungs by rapidly exchanging chloride and bicarbonate ions across the membrane. In collaboration with the Clarke Lab at Columbia University and using molecular dynamics simulations and advanced enhanced-sampling techniques with NAMD, the Resource researchers revealed the mechanism by which depletion of the anionic lipid PIP2 significantly lowers the rate of the transporter. Analysis of the simulations in VMD uncovered that the formation of a salt bridge between the lipid and AE1 residues modulates the transporter's structural dynamics and function. More details can be found in our preprint on bioRxiv.