Residues within transmembrane domains 4 and 6 of the Na,K-ATPase alpha subunit are important for Na+ selectivity

Biochemistry
G Sánchez, G Blanco

Abstract

The Na,K- and H,K-ATPases are plasma membrane enzymes responsible for the active exchange of extracellular K(+) for cytoplasmic Na(+) or H(+), respectively. At present, the structural determinants for the specific function of these ATPases remain poorly understood. To investigate the cation selectivity of these ATPases, we constructed a series of Na,K-ATPase mutants in which residues in the membrane spanning segments of the alpha subunit were changed to the corresponding residues common to gastric H,K-ATPases. Thus, mutants were created with substitutions in transmembrane domains TM1, TM4, TM5, TM6, TM7, and TM8 independently or together (designated TMAll). The function of each mutant was assessed after coexpression with the beta subunit in Sf-9 cells using baculoviruses. The enzymatic properties of TM1, TM7, and TM8 mutants were similar to the wild-type Na,K-ATPase, and while TM5 showed modest changes in apparent affinity for Na(+), TM4, TM6, and TMAll displayed an abnormal activity. This resulted in a Na(+)-independent hydrolysis of ATP, a 2-fold higher K(0.5) for Na(+) activation, and the ability to function at low pH. These results suggest a loss of discrimination for Na(+) over H(+) for the enzymes. In addition, TM4, TM6, ...Continue Reading

References

Apr 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A A McDonoughR A Farley
Mar 1, 1993·The Journal of Physiology·I M Glynn
Mar 29, 1996·The Journal of Biological Chemistry·M CougnonF Jaisser
Nov 22, 1996·The Journal of Biological Chemistry·T A KuntzweilerJ B Lingrel
Oct 6, 1997·The Journal of Biological Chemistry·R BlosteinJ B Lingrel
Jun 22, 1999·The Journal of Biological Chemistry·R BlosteinM J Caplan
Jul 30, 1999·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·R Blostein
May 23, 2001·Archives of Biochemistry and Biophysics·S J RulliE C Rabon
Jun 5, 2002·Annual Review of Biochemistry·Jack H Kaplan
Jan 14, 2003·Annual Review of Physiology·Peter L JorgensenSteven J D Karlish

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Citations

Nov 3, 2005·Reproduction : the Official Journal of the Society for the Study of Fertility·K WagonerG Blanco
Mar 25, 2014·Materials Science & Engineering. C, Materials for Biological Applications·Jinhua LiuKaimin Shih

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