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Proc Natl Acad Sci U S A
1993 Dec 15;9024:11658-62.
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Evidence that facilitative glucose transporters may fold as beta-barrels.
Fischbarg J
,
Cheung M
,
Czegledy F
,
Li J
,
Iserovich P
,
Kuang K
,
Hubbard J
,
Garner M
,
Rosen OM
,
Golde DW
.
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A widely accepted model for the structure of the facilitative glucose transporters (GLUTs) predicts that they form 12 transmembrane alpha-helices and that the highly conserved sequence Ile-386-Ala-405 in GLUT1 is intracellular. We raised a polyclonal antibody against a synthetic peptide encompassing this conserved sequence and found that antibody treatment increased 2-deoxy-D-glucose (DOG) uptake in Xe-nopus oocytes expressing GLUT1, GLUT2, or GLUT4 only when applied to the extracellular side. This effect was dose dependent and was specifically blocked by competition with the peptide Ile-386-Ala-405; it was due to a decrease in the Km for the transport of DOG. To ascertain GLUT orientation, we raised anti-peptide antibodies against the last 21 and 25 C-terminal amino acids of GLUT1 and GLUT4, respectively, which were previously shown to be intracellular. These antibodies increased DOG uptake when injected into oocytes expressing GLUT1 and GLUT4, but not when added extracellularly. Prompted by the noted discrepancy, we found sequence similarity between GLUTs and porins, two of which are known from crystallography to form 16-stranded transmembrane antiparallel beta-barrels. Analysis of the hydrophobicity, amphiphilicity, and turn propensity of GLUT1 leads us to propose that GLUTs fold as porin-like transmembrane beta-barrels. This model is consistent with the results of the present antibody studies and also with previously published experimental evidence inconsistent with the 12-helix model.
Alvarez,
Fourier transform infrared spectroscopic study of the structure and conformational changes of the human erythrocyte glucose transporter.
1987, Pubmed
Alvarez,
Fourier transform infrared spectroscopic study of the structure and conformational changes of the human erythrocyte glucose transporter.
1987,
Pubmed
Asano,
The role of N-glycosylation of GLUT1 for glucose transport activity.
1991,
Pubmed
Asano,
Glucose binding enhances the papain susceptibility of the intracellular loop of the GLUT1 glucose transporter.
1992,
Pubmed
Carruthers,
The human erythrocyte sugar transporter is also a nucleotide binding protein.
1989,
Pubmed
Carruthers,
Facilitated diffusion of glucose.
1990,
Pubmed
Chin,
Structural basis of human erythrocyte glucose transporter function in reconstituted vesicles.
1986,
Pubmed
Chin,
Structural basis of human erythrocyte glucose transporter function in proteoliposome vesicles: circular dichroism measurements.
1987,
Pubmed
Cowan,
Crystal structures explain functional properties of two E. coli porins.
1992,
Pubmed
Davies,
Site-specific antibodies as probes of the topology and function of the human erythrocyte glucose transporter.
1990,
Pubmed
Deziel,
Phosphorylation of the human erythrocyte glucose transporter by protein kinase C: localization of the site of in vivo and in vitro phosphorylation.
1989,
Pubmed
Eisenberg,
The hydrophobic moment detects periodicity in protein hydrophobicity.
1984,
Pubmed
Fischbarg,
Glucose transporters serve as water channels.
1990,
Pubmed
,
Xenbase
Haris,
Does Fourier-transform infrared spectroscopy provide useful information on protein structures?
1992,
Pubmed
Hashiramoto,
Site-directed mutagenesis of GLUT1 in helix 7 residue 282 results in perturbation of exofacial ligand binding.
1992,
Pubmed
Jung,
Structural basis of human erythrocyte glucose transporter function in reconstituted system. Hydrogen exchange.
1986,
Pubmed
Kyte,
A simple method for displaying the hydropathic character of a protein.
1982,
Pubmed
Matthews,
Comparison of the predicted and observed secondary structure of T4 phage lysozyme.
1975,
Pubmed
Mueckler,
Sequence and structure of a human glucose transporter.
1985,
Pubmed
Needleman,
A general method applicable to the search for similarities in the amino acid sequence of two proteins.
1970,
Pubmed
Nikaido,
Transport proteins in bacteria: common themes in their design.
1992,
Pubmed
Oka,
C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity.
1990,
Pubmed
Park,
Differentiation between transmembrane helices and peripheral helices by the deconvolution of circular dichroism spectra of membrane proteins.
1992,
Pubmed
Parker,
Refined structure of the pore-forming domain of colicin A at 2.4 A resolution.
1992,
Pubmed
Pauptit,
A common channel-forming motif in evolutionarily distant porins.
1991,
Pubmed
Perczel,
Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins.
1991,
Pubmed
Preston,
Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.
1992,
Pubmed
,
Xenbase
Qian,
Predicting the secondary structure of globular proteins using neural network models.
1988,
Pubmed
Rost,
Jury returns on structure prediction.
1992,
Pubmed
Sofue,
Possible multifunction of glucose transporter. Transport of nicotinamide by reconstituted liposomes.
1992,
Pubmed
Vera,
Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid.
1993,
Pubmed
,
Xenbase
Vera,
Reconstitution of an insulin signaling pathway in Xenopus laevis oocytes: coexpression of a mammalian insulin receptor and three different mammalian hexose transporters.
1990,
Pubmed
,
Xenbase
Weiss,
The structure of porin from Rhodobacter capsulatus at 1.8 A resolution.
1991,
Pubmed
Welte,
Prediction of the general structure of OmpF and PhoE from the sequence and structure of porin from Rhodobacter capsulatus. Orientation of porin in the membrane.
1991,
Pubmed
Zhang,
Evidence from oocyte expression that the erythrocyte water channel is distinct from band 3 and the glucose transporter.
1991,
Pubmed
,
Xenbase
