Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations

Research output: Contribution to journalJournal articlepeer-review

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Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations. / Poulsen, Hanne; Nissen, Poul; Mouritsen, Ole G.; Khandelia, Himanshu.

In: Journal of Biological Chemistry, Vol. 287, No. 19, 2012, p. 15959-15965.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Poulsen, H, Nissen, P, Mouritsen, OG & Khandelia, H 2012, 'Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations', Journal of Biological Chemistry, vol. 287, no. 19, pp. 15959-15965. https://doi.org/10.1074/jbc.M112.340406

APA

Poulsen, H., Nissen, P., Mouritsen, O. G., & Khandelia, H. (2012). Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations. Journal of Biological Chemistry, 287(19), 15959-15965. https://doi.org/10.1074/jbc.M112.340406

Vancouver

Poulsen H, Nissen P, Mouritsen OG, Khandelia H. Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations. Journal of Biological Chemistry. 2012;287(19):15959-15965. https://doi.org/10.1074/jbc.M112.340406

Author

Poulsen, Hanne ; Nissen, Poul ; Mouritsen, Ole G. ; Khandelia, Himanshu. / Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 19. pp. 15959-15965.

Bibtex

@article{e3b21517c01d4e09aadb902d1b23e5a7,
title = "Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations",
abstract = "Phosphorylation is one of the major mechanisms for post-transcriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all-atom Molecular Dynamics simulations to investigate the structural consequences of phosphorylating the Na+/K+-ATPase (NKA) residue Ser936, which is the best characterized phosphorylation site in NKA, targeted in vivo by protein kinase A (PKA). The Molecular Dynamics simulations suggest that Ser 936 phosphorylation opens a C-terminal hydrated pathway leading to Asp926, a transmembrane residue proposed to form part of the third sodium ion-binding site. Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic the effects of Ser936 phosphorylation. The results establish a structural association of Ser 936 with the C terminus of NKA and indicate that phosphorylation of Ser936 can modulate pumping activity by changing the accessibility to the ion-binding site.",
author = "Hanne Poulsen and Poul Nissen and Mouritsen, {Ole G.} and Himanshu Khandelia",
year = "2012",
doi = "10.1074/jbc.M112.340406",
language = "English",
volume = "287",
pages = "15959--15965",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "19",

}

RIS

TY - JOUR

T1 - Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations

AU - Poulsen, Hanne

AU - Nissen, Poul

AU - Mouritsen, Ole G.

AU - Khandelia, Himanshu

PY - 2012

Y1 - 2012

N2 - Phosphorylation is one of the major mechanisms for post-transcriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all-atom Molecular Dynamics simulations to investigate the structural consequences of phosphorylating the Na+/K+-ATPase (NKA) residue Ser936, which is the best characterized phosphorylation site in NKA, targeted in vivo by protein kinase A (PKA). The Molecular Dynamics simulations suggest that Ser 936 phosphorylation opens a C-terminal hydrated pathway leading to Asp926, a transmembrane residue proposed to form part of the third sodium ion-binding site. Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic the effects of Ser936 phosphorylation. The results establish a structural association of Ser 936 with the C terminus of NKA and indicate that phosphorylation of Ser936 can modulate pumping activity by changing the accessibility to the ion-binding site.

AB - Phosphorylation is one of the major mechanisms for post-transcriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all-atom Molecular Dynamics simulations to investigate the structural consequences of phosphorylating the Na+/K+-ATPase (NKA) residue Ser936, which is the best characterized phosphorylation site in NKA, targeted in vivo by protein kinase A (PKA). The Molecular Dynamics simulations suggest that Ser 936 phosphorylation opens a C-terminal hydrated pathway leading to Asp926, a transmembrane residue proposed to form part of the third sodium ion-binding site. Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic the effects of Ser936 phosphorylation. The results establish a structural association of Ser 936 with the C terminus of NKA and indicate that phosphorylation of Ser936 can modulate pumping activity by changing the accessibility to the ion-binding site.

U2 - 10.1074/jbc.M112.340406

DO - 10.1074/jbc.M112.340406

M3 - Journal article

C2 - 22433860

AN - SCOPUS:84860850396

VL - 287

SP - 15959

EP - 15965

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 19

ER -

ID: 230975237