Back to Search Start Over

Structure and mechanism of the mammalian fructose transporter GLUT5.

Authors :
Nomura, Norimichi
Verdon, Grégory
Kang, Hae Joo
Shimamura, Tatsuro
Nomura, Yayoi
Sonoda, Yo
Hussien, Saba Abdul
Qureshi, Aziz Abdul
Coincon, Mathieu
Sato, Yumi
Abe, Hitomi
Nakada-Nakura, Yoshiko
Hino, Tomoya
Arakawa, Takatoshi
Kusano-Arai, Osamu
Iwanari, Hiroko
Murata, Takeshi
Kobayashi, Takuya
Hamakubo, Takao
Kasahara, Michihiro
Source :
Nature; 10/15/2015, Vol. 526 Issue 7573, p397-401, 5p, 9 Diagrams, 2 Charts, 4 Graphs
Publication Year :
2015

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00280836
Volume :
526
Issue :
7573
Database :
Complementary Index
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
110359644
Full Text :
https://doi.org/10.1038/nature14909