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

DOI: 10.26508/lsa.202000858 DOI Help

Authors: Tania Filipa Custodio (Aarhus University) , Peter Aasted Paulsen (Aarhus University) , Kelly May Frain (Aarhus University) , Bjorn Panyella Pedersen (Aarhus University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Life Science Alliance , VOL 4

State: Published (Approved)
Published: February 2021
Diamond Proposal Number(s): 23316 , 17844 , 13062

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.

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: Max IV Laboratory; DESY-PETRA III; Swiss Light Source

Added On: 10/02/2021 09:38


Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)