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Biophys J
2009 Jan 01;962:748-60. doi: 10.1016/j.bpj.2008.09.045.
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Effects on conformational states of the rabbit sodium/glucose cotransporter through modulation of polarity and charge at glutamine 457.
Liu T
,
Krofchick D
,
Silverman M
.
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The high affinity sodium/glucose cotransporter (SGLT1) couples transport of Na(+) and glucose. Previous studies established that mutant Q457C human SGLT1 retains full activity, and sugar translocation is abolished in mutant Q457R or in mutant Q457C after reaction with methanethiosulfonate derivatives, but Na(+) and sugar binding remain intact. To explore the mechanism by which modulation of Q457 abolishes transport, Q457C and Q457R of rabbit SGLT1 were studied using chemical modification and the two-electrode voltage-clamp technique. Compared to wild-type SGLT1, Q457C exhibits approximately 20-fold reduction in phloridzin affinity and preferential occupancy of an inward-facing state. Alkylation of Q457C by [(2-trimethylammonium) ethyl] methanethiosulphonate bromide, (MTSET), reverses these changes while blocking transport. Analysis of pre-steady-state currents in the absence of sugar yields three decay constants for each of Q457C, Q457C-MTSET and Q457R. Comparison of Q457C-MTSET and Q457R with Q457C and wild-type, reveals that inhibition of transport is accompanied by a decrease in magnitude and voltage-independence of the slow decay constant at negative potentials. But fast and medium decays remain unchanged. Computer simulation of transient currents suggests that introduction of positive charge at position 457 leads to a predominant outward rather than inward-facing conformational state. Taken together, the results suggest that glutamine 457, in addition to being involved in sugar binding, is a residue that is sensitive to conformational changes of the carrier.
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
Althoff,
Na+ -D-glucose cotransporter in the kidney of Leucoraja erinacea: molecular identification and intrarenal distribution.
2007,
Pubmed
,
Xenbase
Balen,
Revised immunolocalization of the Na+-D-glucose cotransporter SGLT1 in rat organs with an improved antibody.
2008,
Pubmed
Chen,
Fast voltage clamp discloses a new component of presteady-state currents from the Na(+)-glucose cotransporter.
1996,
Pubmed
,
Xenbase
Chen,
Sodium leak pathway and substrate binding order in the Na+-glucose cotransporter.
1997,
Pubmed
,
Xenbase
Díez-Sampedro,
Residue 457 controls sugar binding and transport in the Na(+)/glucose cotransporter.
2001,
Pubmed
,
Xenbase
Gagnon,
Effect of substrate on the pre-steady-state kinetics of the Na(+)/glucose cotransporter.
2007,
Pubmed
,
Xenbase
Gagnon,
Voltage-clamp fluorometry in the local environment of the C255-C511 disulfide bridge of the Na+/glucose cotransporter.
2007,
Pubmed
,
Xenbase
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
,
Xenbase
Hirayama,
Common mechanisms of inhibition for the Na+/glucose (hSGLT1) and Na+/Cl-/GABA (hGAT1) cotransporters.
2001,
Pubmed
,
Xenbase
Hirsh,
Cholecystokinin decreases intestinal hexose absorption by a parallel reduction in SGLT1 abundance in the brush-border membrane.
1998,
Pubmed
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
,
Xenbase
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
Liu,
Transmembrane IV of the high-affinity sodium-glucose cotransporter participates in sugar binding.
2008,
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
Loland,
Identification of intracellular residues in the dopamine transporter critical for regulation of transporter conformation and cocaine binding.
2004,
Pubmed
Loo,
Perturbation analysis of the voltage-sensitive conformational changes of the Na+/glucose cotransporter.
2005,
Pubmed
,
Xenbase
Loo,
Conformational changes couple Na+ and glucose transport.
1998,
Pubmed
,
Xenbase
Loo,
Conformational dynamics of hSGLT1 during Na+/glucose cotransport.
2006,
Pubmed
,
Xenbase
Loo,
Relaxation kinetics of the Na+/glucose cotransporter.
1993,
Pubmed
,
Xenbase
MacAulay,
Residues in the extracellular loop 4 are critical for maintaining the conformational equilibrium of the gamma-aminobutyric acid transporter-1.
2003,
Pubmed
,
Xenbase
Martín,
Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption.
1996,
Pubmed
,
Xenbase
Meinild,
Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporter.
2002,
Pubmed
,
Xenbase
Panayotova-Heiermann,
Five transmembrane helices form the sugar pathway through the Na+/glucose cotransporter.
1997,
Pubmed
,
Xenbase
Panayotova-Heiermann,
Sodium/D-glucose cotransporter charge movements involve polar residues.
1994,
Pubmed
,
Xenbase
Parent,
Electrogenic properties of the cloned Na+/glucose cotransporter: I. Voltage-clamp studies.
1992,
Pubmed
,
Xenbase
Parent,
Electrogenic properties of the cloned Na+/glucose cotransporter: II. A transport model under nonrapid equilibrium conditions.
1992,
Pubmed
Pinkett,
An inward-facing conformation of a putative metal-chelate-type ABC transporter.
2007,
Pubmed
Puntheeranurak,
Three surface subdomains form the vestibule of the Na+/glucose cotransporter SGLT1.
2007,
Pubmed
Turk,
Membrane topology motifs in the SGLT cotransporter family.
1997,
Pubmed
Tyagi,
D-Glucose-recognition and phlorizin-binding sites in human sodium/D-glucose cotransporter 1 (hSGLT1): a tryptophan scanning study.
2007,
Pubmed
