Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family.

ABSTRACT: 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 Å 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 "SP 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 modulat

SUBMITTER: Custodio TF 

PROVIDER: S-EPMC7898563 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature