钠-葡萄糖共转运蛋白的结构机制研究进展  

Progress on the mechanism of Sodium-glucose cotransporter

作　　者：崔文浩 孙泽健 陈雷[1] CUI WenHao;SUN ZeJian;CHEN Lei(National Biomedical Imaging Center,Beijing Key Laboratory of Cardiometabolic Molecular Medicine,State Key Laboratory of Membrane Biology,Institute of Molecular Medicine,College of Future Technology,Peking University,Beijing 100871,China)

机构地区：[1]北京大学未来技术学院分子医学研究所,膜生物学国家重点实验室,代谢及心血管分子医学北京市重点实验室,国家生物医学成像科学中心,北京100871

出　　处：《中国科学：生命科学》2024年第8期1337-1345,共9页Scientia Sinica(Vitae)

摘　　要：钠-葡萄糖共转运蛋白(sodium-glucose cotransporters, SGLT)是溶质载体转运蛋白(solute carrier transporter,SLC transporter)超家族的一员,它们能够利用细胞膜内外存在的钠离子的电化学势驱动葡萄糖从低浓度到高浓度跨膜运输. SGLT家族中最重要的两个成员是SGLT1和SGLT2,分布在肾脏和小肠上皮等组织.目前SGLT2已经成为治疗糖尿病的重要靶点, SGLT1抑制剂也有治疗糖尿病和便秘等疾病的潜力.随着冷冻电子显微镜技术的发展, SGLT与辅助蛋白(例如MAP17)形成的复合体、与小分子抑制剂形成的复合物,以及在转运过程中的多个构象的结构均已经被解析.这些研究有助于理解SGLT的转运机制以及药理学性质,也为基于结构的药物研发及优化奠定了基础.Sodium-glucose cotransporter (SGLT) belongs to the solute carrier transporter (SLC transporter) superfamily. SGLT can utilize theelectrochemical gradient of sodium ions across the plasma membrane to drive the uptake of glucose against its concentration gradient.The two most important members of the SGLT family are SGLT1 and SGLT2, which are distributed in tissues such as the kidney andsmall intestine. SGLT2 is an important target for the treatment of diabetes and heart failure. SGLT1 inhibitors hold the potential totreat diabetes, constipation, and other diseases. With the advancement of cryo-EM technology, the structures of SGLT in complexwith auxiliary protein MAP17, the structures of SGLT bound with different small molecule inhibitors, as well as the conformationalchanges of SGLT during transportation, have been resolved. These studies advance our understanding of the transportationmechanism and pharmacology of SGLT and will facilitate future structure-based drug optimization.

关 键 词：SGLT 葡萄糖 转运机制 结构 

分 类 号：R346[医药卫生—基础医学]