RT Journal Article
SR Electronic
T1 Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000858
DO 10.26508/lsa.202000858
VO 4
IS 4
A1 Tânia Filipa Custódio
A1 Peter Aasted Paulsen
A1 Kelly May Frain
A1 Bjørn Panyella Pedersen
YR 2021
UL https://www.life-science-alliance.org/content/4/4/e202000858.abstract
AB 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 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 SP family.