Tracing cytoplasmic Ca(2+) ion and water access points in the Ca(2+)-ATPase.

Biophysical Journal
Maria MusgaardEmad Tajkhorshid

Abstract

Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) transports two Ca(2+) ions across the membrane of the sarco(endo)plasmic reticulum against the concentration gradient, harvesting the required energy by hydrolyzing one ATP molecule during each transport cycle. Although SERCA is one of the best structurally characterized membrane transporters, it is still largely unknown how the transported Ca(2+) ions reach their transmembrane binding sites in SERCA from the cytoplasmic side. Here, we performed extended all-atom molecular dynamics simulations of SERCA. The calculated electrostatic potential of the protein reveals a putative mechanism by which cations may be attracted to and bind to the Ca(2+)-free state of the transporter. Additional molecular dynamics simulations performed on a Ca(2+)-bound state of SERCA reveal a water-filled pathway that may be used by the Ca(2+) ions to reach their buried binding sites from the cytoplasm. Finally, several residues that are involved in attracting and guiding the cations toward the possible entry channel are identified. The results point to a single Ca(2+) entry site close to the kinked part of the first transmembrane helix, in a region loaded with negatively charged residues. From this poin...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 7, 1998·Journal of Molecular Evolution·K B Axelsen, M G Palmgren
Jun 8, 2001·The Biochemical Journal·A G Lee, J M East
Aug 9, 2002·Nature·Chikashi Toyoshima, Hiromi Nomura
Feb 3, 2004·The Journal of Biological Chemistry·Anja Pernille EinholmJens Peter Andersen
Jun 12, 2004·Science·Thomas Lykke-Møller SørensenPoul Nissen
Sep 24, 2004·The Journal of Biological Chemistry·Thomas Lykke-Møller SørensenPoul Nissen
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Jan 7, 2006·Bioinformatics·Mikhail A LomizeHenry I Mosberg
Oct 2, 2007·Biochimica Et Biophysica Acta·Eeva-Liisa KarjalainenAndreas Barth
Dec 14, 2007·Nature·Claus OlesenPoul Nissen
Mar 18, 2009·The Journal of Biological Chemistry·Mette LaursenJ Preben Morth
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yuji SugitaChikashi Toyoshima
May 11, 2011·Nature Communications·Yonathan SonntagLea Thøgersen
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus

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Citations

Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anna L VestergaardJens Peter Andersen
Feb 13, 2013·The Journal of Biological Chemistry·Maike BublitzPoul Nissen
Jul 23, 2013·Current Opinion in Structural Biology·Chikashi Toyoshima, Flemming Cornelius
Mar 19, 2013·Journal of Molecular Biology·Daniel MattlePoul Nissen
Jul 24, 2012·Protein Science : a Publication of the Protein Society·Peter M Kekenes-HuskeyJ Andrew McCammon
Oct 11, 2014·The Journal of Biological Chemistry·Cédric MontignyMarc le Maire
Jul 28, 2016·Frontiers in Physiology·Jens P AndersenRobert S Molday
Aug 16, 2012·Physical Chemistry Chemical Physics : PCCP·Emma S E Eriksson, Leif A Eriksson
Jun 2, 2015·Journal of the American Chemical Society·L Michel Espinoza-Fonseca, G Lizbeth Ramírez-Salinas
Dec 23, 2014·The Journal of Physical Chemistry. B·Nikolai Smolin, Seth L Robia

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