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

Tânia Filipa Custódio, Peter Aasted Paulsen, Kelly May Frain, Bjørn Panyella Pedersen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

44 Citationer (Scopus)

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 2 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.

OriginalsprogEngelsk
Artikelnummere202000858
TidsskriftLife Science Alliance
Vol/bind4
Nummer4
ISSN2575-1077
DOI
StatusUdgivet - apr. 2021

Fingeraftryk

Dyk ned i forskningsemnerne om 'Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family'. Sammen danner de et unikt fingeraftryk.

Citationsformater