The human glucose transporters GLUT1 and GLUT3 have a central role in glucose uptake as canonical members of the Sugar Porter (SP) family. GLUT1 and GLUT3 share a fully conserved substrate-binding site with identical substrate coordination, but differ significantly in transport affinity in line with their physiological function. Here we present a 2.4 A crystal structure of GLUT1 in an inward open conformation and compare it with GLUT3 using both structural and functional data. Our work shows that interactions between a cytosolic "Sugar Porter motif" and a conserved "A motif" stabilize the outward conformational state and increases substrate apparent affinity. Furthermore, we identify a previously undescribed Cl- ion site in GLUT1 and an endofacial lipid/glucose binding site which modulate GLUT kinetics. The results provide a possible explanation for the difference between GLUT1 and GLUT3 glucose affinity, imply a general model for the kinetic regulation in GLUTs and suggest a physiological function for the defining SP sequence motif in the Sugar Porter family.

中文翻译：

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GLUT1和GLUT3的结构比较揭示了Sugar Porter家族的转运调节机制

人糖转运蛋白GLUT1和GLUT3作为Sugar Porter（SP）家族的典型成员，在葡萄糖吸收中起着核心作用。GLUT1和GLUT3共享一个完全保守的底物结合位点，具有相同的底物配位，但根据它们的生理功能，其转运亲和力显着不同。在这里，我们介绍了向内开放构型的GLUT1的2.4 A晶体结构，并使用结构和功能数据将其与GLUT3进行了比较。我们的工作表明，胞质“糖波特基序”和保守的“ A基序”之间的相互作用稳定了向外的构象状态并增加了底物的表观亲和力。此外，我们确定了GLUT1中先前未描述的Cl-离子位点和调节GLUT动力学的界面脂质/葡萄糖结合位点。