Effects of PKA phosphorylation on the conformation of the Na,K-ATPase regulatory protein FXYD1. Biochim Biophys Acta 2009 Nov;1788(11):2462-70
Date
09/19/2009Pubmed ID
19761758Pubmed Central ID
PMC2778042DOI
10.1016/j.bbamem.2009.09.001Scopus ID
2-s2.0-71149085579 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
FXYD1 (phospholemman) is a member of an evolutionarily conserved family of membrane proteins that regulate the function of the Na,K-ATPase enzyme complex in specific tissues and specific physiological states. In heart and skeletal muscle sarcolemma, FXYD1 is also the principal substrate of hormone-regulated phosphorylation by c-AMP dependent protein kinase A and by protein kinase C, which phosphorylate the protein at conserved Ser residues in its cytoplasmic domain, altering its Na,K-ATPase regulatory activity. FXYD1 adopts an L-shaped alpha-helical structure with the transmembrane helix loosely connected to a cytoplasmic amphipathic helix that rests on the membrane surface. In this paper we describe NMR experiments showing that neither PKA phosphorylation at Ser68 nor the physiologically relevant phosphorylation mimicking mutation Ser68Asp induces major changes in the protein conformation. The results, viewed in light of a model of FXYD1 associated with the Na,K-ATPase alpha and beta subunits, indicate that the effects of phosphorylation on the Na,K-ATPase regulatory activity of FXYD1 could be due primarily to changes in electrostatic potential near the membrane surface and near the Na(+)/K(+) ion binding site of the Na,K-ATPase alpha subunit.
Author List
Teriete P, Thai K, Choi J, Marassi FMAuthor
Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceCyclic AMP-Dependent Protein Kinases
Humans
Membrane Proteins
Molecular Sequence Data
Phosphoproteins
Phosphorylation
Protein Conformation
Sodium-Potassium-Exchanging ATPase
