Access of extracellular cations to their binding sites in Na,K-ATPase: role of the second extracellular loop of the alpha subunit

The Journal of General Physiology
Oihana CapendeguyJean-Daniel Horisberger

Abstract

Na,K-ATPase, the main active transport system for monovalent cations in animal cells, is responsible for maintaining Na(+) and K(+) gradients across the plasma membrane. During its transport cycle it binds three cytoplasmic Na(+) ions and releases them on the extracellular side of the membrane, and then binds two extracellular K(+) ions and releases them into the cytoplasm. The fourth, fifth, and sixth transmembrane helices of the alpha subunit of Na,K-ATPase are known to be involved in Na(+) and K(+) binding sites, but the gating mechanisms that control the access of these ions to their binding sites are not yet fully understood. We have focused on the second extracellular loop linking transmembrane segments 3 and 4 and attempted to determine its role in gating. We replaced 13 residues of this loop in the rat alpha1 subunit, from E314 to G326, by cysteine, and then studied the function of these mutants using electrophysiological techniques. We analyzed the results using a structural model obtained by homology with SERCA, and ab initio calculations for the second extracellular loop. Four mutants were markedly modified by the sulfhydryl reagent MTSET, and we investigated them in detail. The substituted cysteines were more readil...Continue Reading

References

Oct 16, 1986·Nature·M Nakao, D C Gadsby
Nov 1, 1989·The American Journal of Physiology·K GeeringB C Rossier
Apr 1, 1994·The Journal of General Physiology·F JaisserJ D Horisberger
Jan 1, 1993·The Journal of General Physiology·R F Rakowski
Sep 6, 2000·Trends in Biochemical Sciences·J A Killian, G von Heijne
May 4, 2001·Biochimica Et Biophysica Acta·M B Ulmschneider, M S Sansom
Mar 19, 2002·The Journal of Physiology·Jean-Daniel Horisberger, Solange Kharoubi-Hess
Aug 9, 2002·Nature·Chikashi Toyoshima, Hiromi Nomura
Dec 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Haruo Ogawa, Chikashi Toyoshima
Jan 14, 2003·Annual Review of Physiology·Peter L JorgensenSteven J D Karlish
Aug 27, 2003·Biochemistry·Guillermo A YudowskiSteven J D Karlish
Nov 25, 2003·FEBS Letters·Chikashi ToyoshimaYuji Sugita
May 5, 2004·The Journal of Biological Chemistry·Jean-Daniel HorisbergerOlivier Michielin
May 12, 2004·Journal of Molecular Biology·Aaron K ChamberlainJames U Bowie
Jun 11, 2004·Annual Review of Biochemistry·Chikashi Toyoshima, Giuseppe Inesi
Jun 12, 2004·Science·Thomas Lykke-Møller SørensenPoul Nissen
Jan 25, 2005·Journal of Molecular Biology·Erik GransethArne Elofsson
Mar 19, 2005·The Journal of Physiology·Oihana Capendeguy, Jean-Daniel Horisberger
Mar 31, 2005·Biochemical and Biophysical Research Communications·Hiroshi EguchiMasaru Kawamura
Aug 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ciming LiJean-Daniel Horisberger
Dec 22, 2005·Journal of Molecular Biology·Theres FagerbergOlivier Michielin

❮ Previous
Next ❯

Citations

Jan 24, 2008·The Journal of Membrane Biology·Hiroshi EguchiKazuo Takeda
Jan 27, 2016·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Rahma ThabetVincent Leignel
Mar 10, 2009·Blood Cells, Molecules & Diseases·Craig Gatto, Mark Milanick
May 25, 2007·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·L C F SantosR P M Furriel
Mar 5, 2020·Molecular and Cellular Biochemistry·Xiuju LiLarry Fliegel

❮ Previous
Next ❯

Methods Mentioned

BETA
in vitro transcription

Software Mentioned

Ramachandran Plot Quality Results Analysis ( PROCHECK
pCLAMP
PROCHECK
CHARMM

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.