Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2011 Oct 19;1018:1887-95. doi: 10.1016/j.bpj.2011.09.019.
Show Gene links
Show Anatomy links
The structural pathway for water permeation through sodium-glucose cotransporters.
Sasseville LJ
,
Cuervo JE
,
Lapointe JY
,
Noskov SY
.
???displayArticle.abstract???
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: a web-based graphical user interface for CHARMM.
2008,
Pubmed
Jo,
CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes.
2009,
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,
Water pumps.
2002,
Pubmed
Loo,
Cotransport of water by the Na+/glucose cotransporter.
1996,
Pubmed
,
Xenbase
Loo,
Passive water and ion transport by cotransporters.
1999,
Pubmed
,
Xenbase
Meinild,
The human Na+-glucose cotransporter is a molecular water pump.
1998,
Pubmed
,
Xenbase
Naftalin,
Osmotic water transport with glucose in GLUT2 and SGLT.
2008,
Pubmed
Naftalin,
Reassessment of models of facilitated transport and cotransport.
2010,
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