Structure of the Na,K-ATPase Regulatory Protein FXYD1 in Micelles
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- 作者：Peter Teriete ; Carla M. Franzin ; Jungyuen Choi ; Francesca M. Marassi
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：June 12, 2007
- 年：2007
- 卷：46
- 期：23
- 页码：6774 - 6783
- 全文大小：530K
- 年卷期：v.46,no.23(June 12, 2007)
- ISSN：1520-4995
文摘
FXYD1 is a major regulatory subunit of the Na,K-ATPase and the principal substrate ofhormone-regulated phosphorylation by c-AMP dependent protein kinases A and C in heart and skeletalmuscle sarcolemma. It is a member of an evolutionarily conserved family of membrane proteins thatregulate the function of the enzyme complex in a tissue-specific and physiological-state-specific manner.Here, we present the three-dimensional structure of FXYD1 determined in micelles by NMR spectroscopy.Structure determination was made possible by measuring residual dipolar couplings in weakly orientedmicelle samples of the protein. This allowed us to obtain the relative orientations of the helical segmentsand information about the protein dynamics. The structural analysis was further facilitated by the inclusionof distance restraints, obtained from paramagnetic spin label relaxation enhancements, and by refinementwith a micelle depth restraint, derived from paramagnetic Mn line broadening effects. The structure ofFXYD1 provides the foundation for understanding its intra-membrane association with the Na,K-ATPase
subunit and suggests a mechanism whereby the phosphorylation of conserved Ser residues, by proteinkinases A and C, could induce a conformational change in the cytoplasmic domain of the protein tomodulate its interaction with the subunit.
subunit and suggests a mechanism whereby the phosphorylation of conserved Ser residues, by proteinkinases A and C, could induce a conformational change in the cytoplasmic domain of the protein tomodulate its interaction with the subunit.