RGD Reference Report - Structure and mechanism of the mammalian fructose transporter GLUT5. - Rat Genome Database

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Structure and mechanism of the mammalian fructose transporter GLUT5.

Authors: Nomura, N  Verdon, G  Kang, HJ  Shimamura, T  Nomura, Y  Sonoda, Y  Hussien, SA  Qureshi, AA  Coincon, M  Sato, Y  Abe, H  Nakada-Nakura, Y  Hino, T  Arakawa, T  Kusano-Arai, O  Iwanari, H  Murata, T  Kobayashi, T  Hamakubo, T  Kasahara, M  Iwata, S  Drew, D 
Citation: Nomura N, etal., Nature. 2015 Oct 15;526(7573):397-401. doi: 10.1038/nature14909. Epub 2015 Sep 30.
RGD ID: 11035336
Pubmed: PMID:26416735   (View Abstract at PubMed)
PMCID: PMC4618315   (View Article at PubMed Central)
DOI: DOI:10.1038/nature14909   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc2a5Ratfructose binding enablesIDA PMID:26416735UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc2a5  (solute carrier family 2 member 5)


Additional Information