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 journal › Journal article › peer-review
Standard
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 journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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