Crystal structure of a bacterial homologue of glucose transporters GLUT1-4.
Sun, Linfeng 1,2,3,4; Zeng, Xin 1,2,3,4; Yan, Chuangye 1,2,3; Sun, Xiuyun 2; Gong, Xinqi 1,2,3; Rao, Yu 2; Yan, Nieng 1,2,3
[Article]
Nature.
490(7420):361-366, October 18, 2012.
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: 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 A, 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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