Author
Listed:
- Norimichi Nomura
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Grégory Verdon
(Imperial College London
Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus
Research Complex at Harwell, Rutherford Appleton Laboratory)
- Hae Joo Kang
(Imperial College London
Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus
Research Complex at Harwell, Rutherford Appleton Laboratory)
- Tatsuro Shimamura
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Yayoi Nomura
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Yo Sonoda
(Imperial College London)
- Saba Abdul Hussien
(Centre for Biomembrane Research, Stockholm University)
- Aziz Abdul Qureshi
(Centre for Biomembrane Research, Stockholm University)
- Mathieu Coincon
(Centre for Biomembrane Research, Stockholm University)
- Yumi Sato
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Hitomi Abe
(Graduate School of Medicine, Kyoto University)
- Yoshiko Nakada-Nakura
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Tomoya Hino
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project)
- Takatoshi Arakawa
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project)
- Osamu Kusano-Arai
(Research Center for Advanced Science and Technology, University of Tokyo)
- Hiroko Iwanari
(Research Center for Advanced Science and Technology, University of Tokyo)
- Takeshi Murata
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project
Systems and Structural Biology Center, RIKEN)
- Takuya Kobayashi
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project)
- Takao Hamakubo
(Research Center for Advanced Science and Technology, University of Tokyo)
- Michihiro Kasahara
(Laboratory of Biophysics, School of Medicine, Teikyo University)
- So Iwata
(Graduate School of Medicine, Kyoto University
Japan Science and Technology Agency, ERATO, Iwata Human Receptor Crystallography Project
Japan Science and Technology Agency, Research Acceleration Program, Membrane Protein Crystallography Project
Imperial College London)
- David Drew
(Imperial College London
Centre for Biomembrane Research, Stockholm University)
Abstract
The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain tumour cells, and inhibitors are potential drugs for these conditions. Here we describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus in open outward- and open inward-facing conformations, respectively. GLUT5 has a major facilitator superfamily fold like other homologous monosaccharide transporters. On the basis of a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate-binding preference of GLUT5 from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of Escherichia coli XylE suggests that, in addition to global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices TM7 and TM10 underlie a ‘gated-pore’ transport mechanism in such monosaccharide transporters.
Suggested Citation
Norimichi Nomura & Grégory Verdon & Hae Joo Kang & Tatsuro Shimamura & Yayoi Nomura & Yo Sonoda & Saba Abdul Hussien & Aziz Abdul Qureshi & Mathieu Coincon & Yumi Sato & Hitomi Abe & Yoshiko Nakada-Na, 2015.
"Structure and mechanism of the mammalian fructose transporter GLUT5,"
Nature, Nature, vol. 526(7573), pages 397-401, October.
Handle:
RePEc:nat:nature:v:526:y:2015:i:7573:d:10.1038_nature14909
DOI: 10.1038/nature14909
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Cited by:
- Monique R Heitmeier & Richard C Hresko & Rachel L Edwards & Michael J Prinsen & Ma Xenia G Ilagan & Audrey R Odom John & Paul W Hruz, 2019.
"Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein ,"
PLOS ONE, Public Library of Science, vol. 14(5), pages 1-20, May.
- Yafei Yuan & Fang Kong & Hanwen Xu & Angqi Zhu & Nieng Yan & Chuangye Yan, 2022.
"Cryo-EM structure of human glucose transporter GLUT4,"
Nature Communications, Nature, vol. 13(1), pages 1-8, December.
- Albert Suades & Aziz Qureshi & Sarah E. McComas & Mathieu Coinçon & Axel Rudling & Yurie Chatzikyriakidou & Michael Landreh & Jens Carlsson & David Drew, 2023.
"Establishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system,"
Nature Communications, Nature, vol. 14(1), pages 1-16, December.
- Titouan Jaunet-Lahary & Tatsuro Shimamura & Masahiro Hayashi & Norimichi Nomura & Kouta Hirasawa & Tetsuya Shimizu & Masao Yamashita & Naotaka Tsutsumi & Yuta Suehiro & Keiichi Kojima & Yuki Sudo & Ta, 2023.
"Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota,"
Nature Communications, Nature, vol. 14(1), pages 1-15, December.
- Elisabeth Lambert & Ahmad Reza Mehdipour & Alexander Schmidt & Gerhard Hummer & Camilo Perez, 2022.
"Evidence for a trap-and-flip mechanism in a proton-dependent lipid transporter,"
Nature Communications, Nature, vol. 13(1), pages 1-13, December.
- Zilin Shen & Li Xu & Tong Wu & Huan Wang & Qifan Wang & Xiaofei Ge & Fang Kong & Gaoxingyu Huang & Xiaojing Pan, 2024.
"Structural basis for urate recognition and apigenin inhibition of human GLUT9,"
Nature Communications, Nature, vol. 15(1), pages 1-10, December.
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