Molecular mechanisms of transport and inhibition in SGLTs (A05)

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The sodium-dependent glucose transporter 2 (SGLT2) is responsible for 90% of renal glucose absorption and its inhibition has a high clinical relevance. However, the molecular structure of this transporter is yet unknown. In this project, we will investigate the atomic structure of SGLT2 in complex with its substrates and inhibitors by high-resolution cryo-EM and additional state-of-the-art methods. In combination with functional, spectroscopic, and computational studies, we aim to provide a molecular description of sodium coupling, substrate sensing, substrate-dependent regulation, and inhibition of SGLT2 glucose transport in the proximal tubule.