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J Membr Biol
2013 Jun 01;2466:495-511. doi: 10.1007/s00232-013-9564-5.
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Implications of aberrant temperature-sensitive glucose transport via the glucose transporter deficiency mutant (GLUT1DS) T295M for the alternate-access and fixed-site transport models.
Cunningham P
,
Naftalin RJ
.
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In silico glucose docking to the transporter GLUT1 templated to the crystal structure of Escherichia coli XylE, a bacterial homolog of GLUT1-4 (4GBZ.pdb), reveals multiple docking sites. One site in the external vestibule in the exofacial linker between TM7 and -8 is adjacent to a missense T295M and a 4-mer insertion mutation. Glucose docking to the adjacent site is occluded in these mutants. These mutants cause an atypical form of glucose transport deficiency syndrome (GLUT1DS), where transport into the brain is deficient, although unusually transport into erythrocytes at 4 °C appears normal. A model in which glucose traverses the transporter via a network of saturable fixed sites simulates the temperature sensitivity of normal and mutant glucose influx and the mutation-dependent alterations of influx and efflux asymmetry when expressed in Xenopus oocytes at 37 °C. The explanation for the temperature sensitivity is that at 4 °C glucose influx between the external and internal vestibules is slow and causes glucose to accumulate in the external vestibule. This retards net glucose uptake from the external solution via two parallel sites into the external vestibule, consequently masking any transport defect at either one of these sites. At 37 °C glucose transit between the external and internal vestibules is rapid, with no significant glucose buildup in the external vestibule, and thereby unmasks any transport defect at one of the parallel input sites. Monitoring glucose transport in patients' erythrocytes at higher temperatures may improve the diagnostic accuracy of the functional test of GLUT1DS.
Barnett,
Structural requirements for binding to the sugar-transport system of the human erythrocyte.
1973, Pubmed
Barnett,
Structural requirements for binding to the sugar-transport system of the human erythrocyte.
1973,
Pubmed
Brahm,
Kinetics of glucose transport in human erythrocytes.
1983,
Pubmed
Brauchi,
Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8.
2004,
Pubmed
Brockmann,
The expanding phenotype of GLUT1-deficiency syndrome.
2009,
Pubmed
Butterfoss,
Boltzmann-type distribution of side-chain conformation in proteins.
2003,
Pubmed
Carruthers,
Will the original glucose transporter isoform please stand up!
2009,
Pubmed
Clapham,
A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels.
2011,
Pubmed
Cloherty,
Human erythrocyte sugar transport is incompatible with available carrier models.
1996,
Pubmed
Cunningham,
Docking studies show that D-glucose and quercetin slide through the transporter GLUT1.
2006,
Pubmed
Fujii,
T295M-associated Glut1 deficiency syndrome with normal erythrocyte 3-OMG uptake.
2011,
Pubmed
Fujii,
Three Japanese patients with glucose transporter type 1 deficiency syndrome.
2007,
Pubmed
Fung,
First report of GLUT1 deficiency syndrome in Chinese patients with novel and hot spot mutations in SLC2A1 gene.
2011,
Pubmed
Jardetzky,
Simple allosteric model for membrane pumps.
1966,
Pubmed
Jiang,
Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1.
2010,
Pubmed
Kasahara,
Identification of a key residue determining substrate affinity in the human glucose transporter GLUT1.
2009,
Pubmed
Kim,
Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent conformations.
2013,
Pubmed
Klepper,
GLUT1 deficiency syndrome in clinical practice.
2012,
Pubmed
Kosti,
Identification of the substrate recognition and transport pathway in a eukaryotic member of the nucleobase-ascorbate transporter (NAT) family.
2012,
Pubmed
Leitch,
alpha- and beta-monosaccharide transport in human erythrocytes.
2009,
Pubmed
Lieb,
Testing and characterizing the simple carrier.
1974,
Pubmed
Liu,
Thermal instability of ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) channel function: protection by single suppressor mutations and inhibiting channel activity.
2012,
Pubmed
,
Xenbase
Lowe,
The kinetics of glucose transport in human red blood cells.
1986,
Pubmed
Manolescu,
A highly conserved hydrophobic motif in the exofacial vestibule of fructose transporting SLC2A proteins acts as a critical determinant of their substrate selectivity.
2007,
Pubmed
,
Xenbase
Manolescu,
Identification of a hydrophobic residue as a key determinant of fructose transport by the facilitative hexose transporter SLC2A7 (GLUT7).
2005,
Pubmed
,
Xenbase
Miller,
The kinetics of selective biological transport. V. Further data on the erythrocyte-monosaccharide transport system.
1971,
Pubmed
Mueckler,
Sequence and structure of a human glucose transporter.
1985,
Pubmed
Naftalin,
Re-examination of hexose exchanges using rat erythrocytes: evidence inconsistent with a one-site sequential exchange model, but consistent with a two-site simultaneous exchange model.
1994,
Pubmed
Naftalin,
Reassessment of models of facilitated transport and cotransport.
2010,
Pubmed
Naftalin,
Alternating carrier models of asymmetric glucose transport violate the energy conservation laws.
2008,
Pubmed
Naula,
A glucose transporter can mediate ribose uptake: definition of residues that confer substrate specificity in a sugar transporter.
2010,
Pubmed
Pantazopoulou,
The first transmembrane segment (TMS1) of UapA contains determinants necessary for expression in the plasma membrane and purine transport.
2006,
Pubmed
Parmeggiani,
Totally asymmetric simple exclusion process with Langmuir kinetics.
2004,
Pubmed
Rotstein,
Glut1 deficiency: inheritance pattern determined by haploinsufficiency.
2010,
Pubmed
,
Xenbase
SEN,
Determination of the temperature and pH dependence of glucose transfer across the human erythrocyte membrane measured by glucose exit.
1962,
Pubmed
Salas-Burgos,
Predicting the three-dimensional structure of the human facilitative glucose transporter glut1 by a novel evolutionary homology strategy: insights on the molecular mechanism of substrate migration, and binding sites for glucose and inhibitory molecules.
2004,
Pubmed
Seatter,
QLS motif in transmembrane helix VII of the glucose transporter family interacts with the C-1 position of D-glucose and is involved in substrate selection at the exofacial binding site.
1998,
Pubmed
,
Xenbase
Seeliger,
Towards computational specificity screening of DNA-binding proteins.
2011,
Pubmed
Seeliger,
Ligand docking and binding site analysis with PyMOL and Autodock/Vina.
2010,
Pubmed
Singh,
A competitive inhibitor traps LeuT in an open-to-out conformation.
2008,
Pubmed
Soares-Silva,
A substrate translocation trajectory in a cytoplasm-facing topological model of the monocarboxylate/H⁺ symporter Jen1p.
2011,
Pubmed
Sun,
Crystal structure of a bacterial homologue of glucose transporters GLUT1-4.
2012,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Wang,
Functional studies of the T295M mutation causing Glut1 deficiency: glucose efflux preferentially affected by T295M.
2008,
Pubmed
,
Xenbase
Wang,
Functional studies of threonine 310 mutations in Glut1: T310I is pathogenic, causing Glut1 deficiency.
2003,
Pubmed
,
Xenbase
Whitesell,
Activation energy of the slowest step in the glucose carrier cycle: break at 23 degrees C and correlation with membrane lipid fluidity.
1989,
Pubmed
Wong,
Disease-associated Glut1 single amino acid substitute mutations S66F, R126C, and T295M constitute Glut1-deficiency states in vitro.
2007,
Pubmed
