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Am J Physiol Cell Physiol
2008 Jul 01;2951:C64-72. doi: 10.1152/ajpcell.90602.2007.
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Transmembrane IV of the high-affinity sodium-glucose cotransporter participates in sugar binding.
Liu T
,
Lo B
,
Speight P
,
Silverman M
.
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Investigation of the structure/function relationships of the sodium-glucose transporter (SGLT1) is crucial to understanding the cotransporter mechanism. In the present study, we used cysteine-scanning mutagenesis and chemical modification by methanethiosulfonate (MTS) derivatives to test whether predicted transmembrane IV participates in sugar binding. Five charged and polar residues (K139, Q142, T156, K157, and D161) and two glucose/galactose malabsorption missense mutations (I147 and S159) were replaced with cysteine. Mutants I147C, T156C, and K157C exhibited sufficient expression to be studied in detail using the two-electrode voltage-clamp method in Xenopus laevis oocytes and COS-7 cells. I147C was similar in function to wild-type and was not studied further. Mutation of lysine-157 to cysteine (K157C) causes loss of phloridzin and alpha-methyl-D-glucopyranoside (alphaMG) binding. These functions are restored by chemical modification with positively charged (2-aminoethyl) methanethiosulfonate hydrobromide (MTSEA). Mutation of threonine-156 to cysteine (T156C) reduces the affinity of alphaMG and phloridzin for T156C by approximately 5-fold and approximately 20-fold, respectively. In addition, phloridzin protects cysteine-156 in T156C from alkylation by MTSEA. Therefore, the presence of a positive charge or a polar residue at 157 and 156, respectively, affects sugar binding and sugar-induced Na(+) currents.
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003, Pubmed
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003,
Pubmed
Chen,
Fast voltage clamp discloses a new component of presteady-state currents from the Na(+)-glucose cotransporter.
1996,
Pubmed
,
Xenbase
Diez-Sampedro,
A glucose sensor hiding in a family of transporters.
2003,
Pubmed
,
Xenbase
Díez-Sampedro,
Coupled sodium/glucose cotransport by SGLT1 requires a negative charge at position 454.
2004,
Pubmed
,
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Gagnon,
Identification of a disulfide bridge linking the fourth and the seventh extracellular loops of the Na+/glucose cotransporter.
2006,
Pubmed
,
Xenbase
Hirayama,
Sodium-dependent reorganization of the sugar-binding site of SGLT1.
2007,
Pubmed
,
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Huntley,
Position 170 of Rabbit Na+/glucose cotransporter (rSGLT1) lies in the Na+ pathway; modulation of polarity/charge at this site regulates charge transfer and carrier turnover.
2004,
Pubmed
,
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Huntley,
A glutamine to glutamate mutation at position 170 (Q170E) in the rabbit Na+/glucose cotransporter, rSGLT1, enhances binding affinity for Na+.
2006,
Pubmed
,
Xenbase
Krofchick,
Investigating the conformational states of the rabbit Na+/glucose cotransporter.
2003,
Pubmed
,
Xenbase
Lo,
Replacement of Ala-166 with cysteine in the high affinity rabbit sodium/glucose transporter alters transport kinetics and allows methanethiosulfonate ethylamine to inhibit transporter function.
1998,
Pubmed
,
Xenbase
Lo,
Cysteine scanning mutagenesis of the segment between putative transmembrane helices IV and V of the high affinity Na+/Glucose cotransporter SGLT1. Evidence that this region participates in the Na+ and voltage dependence of the transporter.
1998,
Pubmed
,
Xenbase
Loo,
Conformational changes couple Na+ and glucose transport.
1998,
Pubmed
,
Xenbase
Loo,
Perturbation analysis of the voltage-sensitive conformational changes of the Na+/glucose cotransporter.
2005,
Pubmed
,
Xenbase
Meinild,
Evidence for the involvement of Ala 166 in coupling Na(+) to sugar transport through the human Na(+)/glucose cotransporter.
2001,
Pubmed
,
Xenbase
Pajor,
Conformationally sensitive residues in extracellular loop 5 of the Na+/dicarboxylate co-transporter.
2005,
Pubmed
Panayotova-Heiermann,
Five transmembrane helices form the sugar pathway through the Na+/glucose cotransporter.
1997,
Pubmed
,
Xenbase
Panayotova-Heiermann,
Neutralization of conservative charged transmembrane residues in the Na+/glucose cotransporter SGLT1.
1998,
Pubmed
Panayotova-Heiermann,
Sodium/D-glucose cotransporter charge movements involve polar residues.
1994,
Pubmed
,
Xenbase
Puntheeranurak,
Three surface subdomains form the vestibule of the Na+/glucose cotransporter SGLT1.
2007,
Pubmed
Turk,
Membrane topology of the human Na+/glucose cotransporter SGLT1.
1996,
Pubmed
,
Xenbase
Vayro,
Functional studies of the rabbit intestinal Na+/glucose carrier (SGLT1) expressed in COS-7 cells: evaluation of the mutant A166C indicates this region is important for Na+-activation of the carrier.
1998,
Pubmed
Wright,
Active sugar transport in health and disease.
2007,
Pubmed
