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
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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
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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.
Original language | English |
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Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 19 |
Pages (from-to) | 15959-15965 |
Number of pages | 7 |
ISSN | 0021-9258 |
DOIs | |
Publication status | Published - 2012 |
Externally published | Yes |
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