TY - JOUR
T1 - Crystal structure of a bacterial homologue of glucose transporters GLUT1-4
AU - Sun, Linfeng
AU - Zeng, Xin
AU - Yan, Chuangye
AU - Sun, Xiuyun
AU - Gong, Xinqi
AU - Rao, Yu
AU - Yan, Nieng
N1 - Funding Information:
Acknowledgements 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.
PY - 2012/10/18
Y1 - 2012/10/18
N2 - 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 2.6Å, 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.
AB - 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 2.6Å, 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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U2 - 10.1038/nature11524
DO - 10.1038/nature11524
M3 - Article
C2 - 23075985
AN - SCOPUS:84867657593
SN - 0028-0836
VL - 490
SP - 361
EP - 366
JO - Nature
JF - Nature
IS - 7420
ER -