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.
J Membr Biol
2006 Jan 01;2131:1-9. doi: 10.1007/s00232-006-0035-0.
Show Gene links
Show Anatomy links
The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current.
Li C
,
Geering K
,
Horisberger JD
.
???displayArticle.abstract???
Sodium- and potassium-activated adenosine triphosphatases (Na,K-ATPase) is the ubiquitous active transport system that maintains the Na(+) and K(+) gradients across the plasma membrane by exchanging three intracellular Na(+) ions against two extracellular K(+) ions. In addition to the two cation binding sites homologous to the calcium site of sarcoplasmic and endoplasmic reticulum calcium ATPase and which are alternatively occupied by Na(+) and K(+) ions, a third Na(+)-specific site is located close to transmembrane domains 5, 6 and 9, and mutations close to this site induce marked alterations of the voltage-dependent release of Na(+) to the extracellular side. In the absence of extracellular Na(+) and K(+), Na,K-ATPase carries an acidic pH-activated, ouabain-sensitive "leak" current. We investigated the relationship between the third Na(+) binding site and the pH-activated current. The decrease (in E961A, T814A and Y778F mutants) or the increase (in G813A mutant) of the voltage-dependent extracellular Na(+) affinity was paralleled by a decrease or an increase in the pH-activated current, respectively. Moreover, replacing E961 with oxygen-containing side chain residues such as glutamine or aspartate had little effect on the voltage-dependent affinity for extracellular Na(+) and produced only small effects on the pH-activated current. Our results suggest that extracellular protons and Na(+) ions share a high field access channel between the extracellular solution and the third Na(+) binding site.
Apell,
Functional properties of Na,K-ATPase, and their structural implications, as detected with biophysical techniques.
2001, Pubmed
Apell,
Functional properties of Na,K-ATPase, and their structural implications, as detected with biophysical techniques.
2001,
Pubmed
Efthymiadis,
Inward-directed current generated by the Na+,K+ pump in Na(+)- and K(+)-free medium.
1993,
Pubmed
,
Xenbase
Feng,
Functional consequences of substitutions of the carboxyl residue glutamate 779 of the Na,K-ATPase.
1995,
Pubmed
Gadsby,
Extracellular access to the Na,K pump: pathway similar to ion channel.
1993,
Pubmed
Geering,
Oligomerization and maturation of Na,K-ATPase: functional interaction of the cytoplasmic NH2 terminus of the beta subunit with the alpha subunit.
1996,
Pubmed
,
Xenbase
Geering,
The functional role of beta subunits in oligomeric P-type ATPases.
2001,
Pubmed
Girardet,
Immunochemical evidence for a transmembrane orientation of both the (Na+, K+)-ATPase subunits.
1981,
Pubmed
Håkansson,
Homology modeling of Na,K-ATPase: a putative third sodium binding site suggests a relay mechanism compatible with the electrogenic profile of Na+ translocation.
2003,
Pubmed
Hilgemann,
Channel-like function of the Na,K pump probed at microsecond resolution in giant membrane patches.
1994,
Pubmed
Horisberger,
Recent insights into the structure and mechanism of the sodium pump.
2004,
Pubmed
Horisberger,
The fourth transmembrane segment of the Na,K-ATPase alpha subunit: a systematic mutagenesis study.
2004,
Pubmed
,
Xenbase
Horisberger,
Functional differences between alpha subunit isoforms of the rat Na,K-ATPase expressed in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Jaisser,
Modulation of the Na,K-pump function by beta subunit isoforms.
1994,
Pubmed
,
Xenbase
Jewell-Motz,
Site-directed mutagenesis of the Na,K-ATPase: consequences of substitutions of negatively-charged amino acids localized in the transmembrane domains.
1993,
Pubmed
Jorgensen,
Structure and mechanism of Na,K-ATPase: functional sites and their interactions.
2003,
Pubmed
Li,
A third Na+-binding site in the sodium pump.
2005,
Pubmed
,
Xenbase
Melton,
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
1984,
Pubmed
Nagle,
Molecular mechanisms for proton transport in membranes.
1978,
Pubmed
Nelson,
A general method of site-specific mutagenesis using a modification of the Thermus aquaticus polymerase chain reaction.
1989,
Pubmed
Ogawa,
Homology modeling of the cation binding sites of Na+K+-ATPase.
2002,
Pubmed
Pomès,
Molecular mechanism of H+ conduction in the single-file water chain of the gramicidin channel.
2002,
Pubmed
POST,
The linkage of sodium, potassium, and ammonium active transport across the human erythrocyte membrane.
1957,
Pubmed
Rakowski,
A negative slope in the current-voltage relationship of the Na+/K+ pump in Xenopus oocytes produced by reduction of external [K+].
1991,
Pubmed
,
Xenbase
Rettinger,
Characteristics of Na+/K(+)-ATPase mediated proton current in Na(+)- and K(+)-free extracellular solutions. Indications for kinetic similarities between H+/K(+)-ATPase and Na+/K(+)-ATPase.
1996,
Pubmed
,
Xenbase
Sweadner,
Structural similarities of Na,K-ATPase and SERCA, the Ca(2+)-ATPase of the sarcoplasmic reticulum.
2001,
Pubmed
Toyoshima,
Crystal structure of the calcium pump with a bound ATP analogue.
2004,
Pubmed
Toyoshima,
Structural changes in the calcium pump accompanying the dissociation of calcium.
2002,
Pubmed
Toyoshima,
Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution.
2000,
Pubmed
Van Huysse,
Site-directed mutagenesis of a predicted cation binding site of Na, K-ATPase.
1993,
Pubmed
Vasilyev,
Effect of extracellular pH on presteady-state and steady-state current mediated by the Na+/K+ pump.
2004,
Pubmed
,
Xenbase
Wang,
A conformation of Na(+)-K+ pump is permeable to proton.
1995,
Pubmed
,
Xenbase
