6THA

Crystal structure of human sugar transporter GLUT1 (SLC2A1) in the inward conformation

Summary for 6THA

• Entry DOI: 10.2210/pdb6tha/pdb
• Descriptor: Solute carrier family 2, facilitated glucose transporter member 1, nonyl beta-D-glucopyranoside, 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL, ... (5 entities in total)
• Functional Keywords: membrane protein, alpha-helical protein, sugar transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 55566.62

Authors

Pedersen, B.P.,Paulsen, P.A.,Custodio, T.F. (deposition date: 2019-11-19, release date: 2020-11-25, Last modification date: 2024-01-24)

Primary citation

Custodio, T.F.,Paulsen, P.A.,Frain, K.M.,Pedersen, B.P.
Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family.
Life Sci Alliance, 4:-, 2021

PubMed 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 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.

PubMed: 33536238
DOI: 10.26508/lsa.202000858

Experimental method

X-RAY DIFFRACTION (2.4 Å)