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Biophys J
2011 Oct 19;1018:1887-95. doi: 10.1016/j.bpj.2011.09.019.
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The structural pathway for water permeation through sodium-glucose cotransporters.
Sasseville LJ, Cuervo JE, Lapointe JY, Noskov SY.
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Although water permeation across cell membranes occurs through several types of membrane proteins, the only permeation mechanism resolved at atomic scale is that through aquaporins. Crystallization of the Vibrio parahaemolyticus sodium-galactose transporter (vSGLT) allows investigation of putative water permeation pathways through both vSGLT and the homologous human Na-glucose cotransporter (hSGLT1) using computational methods. Grand canonical Monte Carlo and molecular dynamics simulations were used to stably insert water molecules in both proteins, showing the presence of a water-filled pathway composed of ∼100 water molecules. This provides a structural basis for passive water permeation that is difficult to reconcile with the water cotransport hypothesis. Potential-of-mean-force calculations of water going through the crystal structure of vSGLT shows a single barrier of 7.7 kCal mol(-1), in agreement with previously published experimental data for cotransporters of the SGLT family. Electrophysiological and volumetric experiments performed on hSGLT1-expressing Xenopus oocytes showed that the passive permeation pathway exists in different conformational states. In particular, experimental conditions that aim to mimic the conformation of the crystal structure displayed passive water permeability. These results provide groundwork for understanding the structural basis of cotransporter water permeability.
Baker,
Protein structure prediction and structural genomics.
2001, Pubmed
Baker,
Protein structure prediction and structural genomics.
2001,
Pubmed Bissonnette,
Functional expression of tagged human Na+-glucose cotransporter in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase Bourgeois,
Determination of transport stoichiometry for two cation-coupled myo-inositol cotransporters: SMIT2 and HMIT.
2005,
Pubmed
,
Xenbase Brooks,
CHARMM: the biomolecular simulation program.
2009,
Pubmed Canutescu,
A graph-theory algorithm for rapid protein side-chain prediction.
2003,
Pubmed Charron,
Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.
2006,
Pubmed
,
Xenbase Choe,
Water permeation through the sodium-dependent galactose cotransporter vSGLT.
2010,
Pubmed Duquette,
Local osmotic gradients drive the water flux associated with Na(+)/glucose cotransport.
2001,
Pubmed
,
Xenbase Faham,
The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport.
2008,
Pubmed Fischbarg,
Evidence that the glucose transporter serves as a water channel in J774 macrophages.
1989,
Pubmed Gagnon,
Effect of substrate on the pre-steady-state kinetics of the Na(+)/glucose cotransporter.
2007,
Pubmed
,
Xenbase Gagnon,
Glucose accumulation can account for the initial water flux triggered by Na+/glucose cotransport.
2004,
Pubmed
,
Xenbase Ginalski,
Comparative modeling for protein structure prediction.
2006,
Pubmed Jo,
CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes.
2009,
Pubmed Jo,
CHARMM-GUI: a web-based graphical user interface for CHARMM.
2008,
Pubmed Leung,
Functional expression of the Vibrio parahaemolyticus Na+/galactose (vSGLT) cotransporter in Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase Li,
Ion-releasing state of a secondary membrane transporter.
2009,
Pubmed Loike,
Sodium-glucose cotransporters display sodium- and phlorizin-dependent water permeability.
1996,
Pubmed
,
Xenbase Lomize,
OPM: orientations of proteins in membranes database.
2006,
Pubmed Longpré,
The actual ionic nature of the leak current through the Na+/glucose cotransporter SGLT1.
2010,
Pubmed
,
Xenbase Loo,
Cotransport of water by the Na+/glucose cotransporter.
1996,
Pubmed
,
Xenbase Loo,
Passive water and ion transport by cotransporters.
1999,
Pubmed
,
Xenbase Loo,
Water pumps.
2002,
Pubmed Meinild,
The human Na+-glucose cotransporter is a molecular water pump.
1998,
Pubmed
,
Xenbase Naftalin,
Reassessment of models of facilitated transport and cotransport.
2010,
Pubmed Naftalin,
Osmotic water transport with glucose in GLUT2 and SGLT.
2008,
Pubmed Noskov,
Molecular mechanism of substrate specificity in the bacterial neutral amino acid transporter LeuT.
2008,
Pubmed Reuss,
Water transport controversies--an overview.
2002,
Pubmed Schultz,
Epithelial water absorption: osmosis or cotransport?
2001,
Pubmed
,
Xenbase Wang,
Absolute binding free energy calculations using molecular dynamics simulations with restraining potentials.
2006,
Pubmed Watanabe,
The mechanism of sodium and substrate release from the binding pocket of vSGLT.
2010,
Pubmed Woo,
Grand canonical Monte Carlo simulations of water in protein environments.
2004,
Pubmed Wright,
Active sugar transport in health and disease.
2007,
Pubmed Zampighi,
A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase Zeuthen,
Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit.
2001,
Pubmed
,
Xenbase Zeuthen,
Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.
2006,
Pubmed
,
Xenbase Zomot,
The sodium/galactose symporter crystal structure is a dynamic, not so occluded state.
2010,
Pubmed
