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.
Proc Natl Acad Sci U S A
2005 Sep 06;10236:12706-11. doi: 10.1073/pnas.0505980102.
Show Gene links
Show Anatomy links
A third Na+-binding site in the sodium pump.
Li C
,
Capendeguy O
,
Geering K
,
Horisberger JD
.
???displayArticle.abstract???
The sodium pump, or Na,K-ATPase, exports three intracellular sodium ions in exchange for two extracellular potassium ions. In the high resolution structure of the related calcium pump, two cation-binding sites have been identified. The two corresponding sites in the sodium pump are expected to be alternatively occupied by sodium and potassium. The position of a third sodium-specific site is still hypothetical. Here, we report the large effects of single residue substitutions on the voltage-dependent kinetics of the release of sodium to the extracellular side of the membrane. These mutations also alter the apparent affinity for intracellular sodium while one of them does not affect the intrinsic affinity for potassium. These results enable us to locate the third sodium-specific site of the sodium pump in a space between the fifth, sixth, and ninth transmembrane helices of the alpha-subunit and provide an experimental validation of the model proposed by Ogawa and Toyoshima [Ogawa, H. & Toyoshima, C. (2002) Proc. Natl. Acad. Sci. USA 99, 15977-15982].
Canessa,
Mutation of a cysteine in the first transmembrane segment of Na,K-ATPase alpha subunit confers ouabain resistance.
1992, Pubmed,
Xenbase
Canessa,
Mutation of a cysteine in the first transmembrane segment of Na,K-ATPase alpha subunit confers ouabain resistance.
1992,
Pubmed
,
Xenbase
Crambert,
FXYD proteins: new tissue-specific regulators of the ubiquitous Na,K-ATPase.
2003,
Pubmed
De Weer,
Voltage dependence of the apparent affinity for external Na(+) of the backward-running sodium pump.
2001,
Pubmed
Füzesi,
Covalent cross-links between the gamma subunit (FXYD2) and alpha and beta subunits of Na,K-ATPase: modeling the alpha-gamma interaction.
2005,
Pubmed
Gadsby,
Extracellular access to the Na,K pump: pathway similar to ion channel.
1993,
Pubmed
Hasler,
Role of beta-subunit domains in the assembly, stable expression, intracellular routing, and functional properties of Na,K-ATPase.
1998,
Pubmed
,
Xenbase
Hilgemann,
Channel-like function of the Na,K pump probed at microsecond resolution in giant membrane patches.
1994,
Pubmed
Holmgren,
Three distinct and sequential steps in the release of sodium ions by the Na+/K+-ATPase.
2000,
Pubmed
Horisberger,
Functional differences between alpha subunit isoforms of the rat Na,K-ATPase expressed in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Horisberger,
Recent insights into the structure and mechanism of the sodium pump.
2004,
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
Imagawa,
Thr-774 (transmembrane segment M5), Val-920 (M8), and Glu-954 (M9) are involved in Na+ transport, and Gln-923 (M8) is essential for Na,K-ATPase activity.
2005,
Pubmed
Jaisser,
Modulation of the Na,K-pump function by beta subunit isoforms.
1994,
Pubmed
,
Xenbase
James,
Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.
1999,
Pubmed
Jorgensen,
Structure and mechanism of Na,K-ATPase: functional sites and their interactions.
2003,
Pubmed
Li,
Structural and functional interaction sites between Na,K-ATPase and FXYD proteins.
2004,
Pubmed
,
Xenbase
Mahmmoud,
Interaction of FXYD10 (PLMS) with Na,K-ATPase from shark rectal glands. Close proximity of Cys74 of FXYD10 to Cys254 in the a domain of the alpha-subunit revealed by intermolecular thiol cross-linking.
2005,
Pubmed
Nakao,
Voltage dependence of Na translocation by the Na/K pump.
,
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
Olesen,
Dephosphorylation of the calcium pump coupled to counterion occlusion.
2004,
Pubmed
Rakowski,
Charge movement by the Na/K pump in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Sagar,
Access channel model for the voltage dependence of the forward-running Na+/K+ pump.
1994,
Pubmed
,
Xenbase
Shainskaya,
Entrance port for Na(+) and K(+) ions on Na(+),K(+)-ATPase in the cytoplasmic loop between trans-membrane segments M6 and M7 of the alpha subunit. Proximity Of the cytoplasmic segment of the beta subunit.
2000,
Pubmed
Sørensen,
Phosphoryl transfer and calcium ion occlusion in the calcium pump.
2004,
Pubmed
Toyoshima,
Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution.
2000,
Pubmed
Toyoshima,
Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum.
2004,
Pubmed
Toyoshima,
Crystal structure of the calcium pump with a bound ATP analogue.
2004,
Pubmed
Toyoshima,
Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues.
2004,
Pubmed
Van Huysse,
Site-directed mutagenesis of a predicted cation binding site of Na, K-ATPase.
1993,
Pubmed
Vasilets,
Voltage-dependent inhibition of the sodium pump by external sodium: species differences and possible role of the N-terminus of the alpha-subunit.
1993,
Pubmed
,
Xenbase
Wang,
Role in cation translocation of the N-terminus of the alpha-subunit of the Na(+)-K+ pump of Bufo.
1996,
Pubmed
,
Xenbase
