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


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.

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Figure 1: The structure of XylE bound to d -xylose has an outward-facing, partly occluded conformation.
Figure 2: Recognition of d -xylose by XylE.
Figure 3: Coordination of d -glucose by XylE.
Figure 4: Homology-based modelling of GLUT1 structure.
Figure 5: Functional significance of the conserved SP family signature motifs.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

The atomic coordinates and structure factors of XylE bound to d-xylose, d-glucose and 6-BrGlc are deposited in the Protein Data Bank with accession codes 4GBY, 4GBZ and 4GC0.


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We thank J. He, L. Tang, F. Yu and S. Huang at Shanghai Synchrotron Radiation Facility, and K. Hasegawa and T. Kumasaka at the SPring-8 beamline BL41XU, for on-site assistance. This work was supported by funds from the Ministry of Science and Technology (grant numbers 2009CB918802 and 2011CB910501), projects 31125009 and 91017011 of the National Natural Science Foundation of China, and funds from Tsinghua University.

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L.S., X.Z. and N.Y. designed all experiments. L.S., X.Z., C.Y., X.G. and N.Y. performed the experiments for structural determination, homology-based structure modelling and biochemical analysis. X.S. and Y.R. synthesized 6-BrGlc. All authors analysed the data and contributed to manuscript preparation. N.Y. wrote the manuscript.

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Correspondence to Nieng Yan.

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Sun, L., Zeng, X., Yan, C. et al. Crystal structure of a bacterial homologue of glucose transporters GLUT1–4. Nature 490, 361–366 (2012).

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