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.
State Key Laboratory of Bio-membrane and Membrane Biotechnology, Center for Structural Biology, Tsinghua University, Beijing 100084, China.
Linfeng
L
Sun
Xin
X
Zeng
Chuangye
C
Yan
Xiuyun
X
Sun
Xinqi
X
Gong
Yu
Y
Rao
Nieng
N
Yan
D001692:Biological Transport; D018360:Crystallography, X-Ray; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry* / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D027981:Symporters / Q000737:chemistry* / Q000378:metabolism; D014994:Xylose / Q000737:chemistry / Q000378:metabolism
C576549:6-bromo-6-deoxy-D-glucose; D029968:Escherichia coli Proteins; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D027981:Symporters; C033903:xylE protein, E coli; D003847:Deoxyglucose; D014994:Xylose; D005947:Glucose