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.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Biological Chemistry |
Vol/bind | 287 |
Udgave nummer | 19 |
Sider (fra-til) | 15959-15965 |
Antal sider | 7 |
ISSN | 0021-9258 |
DOI | |
Status | Udgivet - 2012 |
Eksternt udgivet | Ja |
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