Molecular mechanisms of transport and inhibition in SGLTs (A05)

钠依赖性葡萄糖转运蛋白2（SGLT 2）负责90%的肾脏葡萄糖吸收，其抑制具有高度临床相关性。然而，这种转运蛋白的分子结构尚不清楚。在本项目中，我们将通过高分辨率cryo-EM和其他最先进的方法研究SGLT 2与其底物和抑制剂复合的原子结构。结合功能，光谱和计算研究，我们的目标是提供钠偶联，底物传感，底物依赖性调节和抑制SGLT 2葡萄糖转运在近端小管的分子描述。

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.