|Title||Crystal structure of a bacterial homologue of glucose transporters GLUT1-4.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Sun, L, Zeng, X, Yan, C, Sun, X, Gong, X, Rao, Y, Yan, N|
|Date Published||2012 Oct 18|
|Keywords||Biological Transport, Crystallography, X-Ray, Deoxyglucose, Escherichia coli, Escherichia coli Proteins, Glucose, Glucose Transport Proteins, Facilitative, Glucose Transporter Type 1, Humans, Hydrogen Bonding, Models, Molecular, Protein Conformation, Structural Homology, Protein, Structure-Activity Relationship, Substrate Specificity, Symporters, Xylose|
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.