Structure and mechanism of the mammalian fructose transporter GLUT5

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-Nakura, Tomoya Hino, Takatoshi Arakawa, Osamu Kusano-Arai, Hiroko Iwanari, Takeshi Murata, Takuya Kobayashi, Takao Hamakubo, Michihiro Kasahara, So Iwata () and David Drew ()
Additional contact information
Norimichi Nomura: Graduate School of Medicine, Kyoto University
Grégory Verdon: Imperial College London
Hae Joo Kang: Imperial College London
Tatsuro Shimamura: Graduate School of Medicine, Kyoto University
Yayoi Nomura: Graduate School of Medicine, Kyoto University
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
Hitomi Abe: Graduate School of Medicine, Kyoto University
Yoshiko Nakada-Nakura: Graduate School of Medicine, Kyoto University
Tomoya Hino: Graduate School of Medicine, Kyoto University
Takatoshi Arakawa: Graduate School of Medicine, Kyoto University
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
Takuya Kobayashi: Graduate School of Medicine, Kyoto University
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
David Drew: Imperial College London

Nature, 2015, vol. 526, issue 7573, 397-401

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/nature14909 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:526:y:2015:i:7573:d:10.1038_nature14909

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature14909

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().