Open AccessA third Na + -binding site in the sodium pump
Author(s) -
Ciming Li,
Oihana Capendeguy,
Käthi Geering,
JeanDaniel Horisberger
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0505980102
Subject(s) - sodium , chemistry , binding site , sodium pump , biochemistry , organic chemistry , ouabain
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].