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Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898563/ https://www.ncbi.nlm.nih.gov/pubmed/33536238 http://dx.doi.org/10.26508/lsa.202000858 |
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author | Custódio, Tânia Filipa Paulsen, Peter Aasted Frain, Kelly May Pedersen, Bjørn Panyella |
author_facet | Custódio, Tânia Filipa Paulsen, Peter Aasted Frain, Kelly May Pedersen, Bjørn Panyella |
author_sort | Custódio, Tânia Filipa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7898563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-78985632021-03-23 Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family Custódio, Tânia Filipa Paulsen, Peter Aasted Frain, Kelly May Pedersen, Bjørn Panyella Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2021-02-03 /pmc/articles/PMC7898563/ /pubmed/33536238 http://dx.doi.org/10.26508/lsa.202000858 Text en © 2021 Custódio et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Custódio, Tânia Filipa Paulsen, Peter Aasted Frain, Kelly May Pedersen, Bjørn Panyella Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title | Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title_full | Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title_fullStr | Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title_full_unstemmed | Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title_short | Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family |
title_sort | structural comparison of glut1 to glut3 reveal transport regulation mechanism in sugar porter family |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898563/ https://www.ncbi.nlm.nih.gov/pubmed/33536238 http://dx.doi.org/10.26508/lsa.202000858 |
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