Crystal structure of a bacterial homologue of glucose transporters GLUT1-4

Nature. 2012 Oct 18;490(7420):361-6. doi: 10.1038/nature11524.


Glucose transporters are essential for metabolism of glucose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4. Despite rigorous efforts, the structural information for GLUT1-4 or their homologues remains largely unknown. Here we report three related crystal structures of XylE, an Escherichia coli homologue of GLUT1-4, in complex with d-xylose, d-glucose and 6-bromo-6-deoxy-D-glucose, at resolutions of 2.8, 2.9 and 2.6 Å, respectively. The structure consists of a typical major facilitator superfamily fold of 12 transmembrane segments and a unique intracellular four-helix domain. XylE was captured in an outward-facing, partly occluded conformation. Most of the important amino acids responsible for recognition of D-xylose or d-glucose are invariant in GLUT1-4, suggesting functional and mechanistic conservations. Structure-based modelling of GLUT1-4 allows mapping and interpretation of disease-related mutations. The structural and biochemical information reported here constitutes an important framework for mechanistic understanding of glucose transporters and sugar porters in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Crystallography, X-Ray
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / chemistry
  • Deoxyglucose / metabolism
  • Escherichia coli / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Glucose / chemistry
  • Glucose / metabolism
  • Glucose Transport Proteins, Facilitative / chemistry*
  • Glucose Transport Proteins, Facilitative / metabolism
  • Glucose Transporter Type 1 / chemistry
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Protein Conformation
  • Structural Homology, Protein
  • Structure-Activity Relationship
  • Substrate Specificity
  • Symporters / chemistry*
  • Symporters / metabolism
  • Xylose / chemistry
  • Xylose / metabolism


  • 6-bromo-6-deoxy-D-glucose
  • Escherichia coli Proteins
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • Symporters
  • xylE protein, E coli
  • Deoxyglucose
  • Xylose
  • Glucose

Associated data

  • PDB/4GBY
  • PDB/4GBZ
  • PDB/4GC0