Change search
ReferencesLink to record
Permanent link

Direct link
Structure and mechanism of the mammalian fructose transporter GLUT5
Show others and affiliations
Number of Authors: 22
2015 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7573, 397-+ p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 526, no 7573, 397-+ p.
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-122925DOI: 10.1038/nature14909ISI: 000362730200044OAI: diva2:871665
Available from: 2015-11-16 Created: 2015-11-11 Last updated: 2015-11-16Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Hussien, Saba AbdulQureshi, Aziz AbdulCoincon, MathieuDrew, David
By organisation
Department of Biochemistry and Biophysics
In the same journal
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 25 hits
ReferencesLink to record
Permanent link

Direct link