期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 49, 页码 33850-33861出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.590307
关键词
Calcium ATPase; Mass Spectrometry (MS); Membrane Protein; Protein Acylation; Protein Palmitoylation; Sarcoplasmic Reticulum (SR); Protein Oleoylation; Sarcolipin
资金
- Agence Nationale de la Recherche
- Domaines d'Interet Majeur Maladies Infectieuses Region Ile de France
Background: Many functions are subjected to regulation by protein-protein interactions. An example is the SERCA1a-SLN8 complex. Results: Rabbit and pig SLN have two types of fatty acid anchors (palmitic and oleic acid) attached to an intramembranous cysteine residue. Conclusion: A role and evolutionary significance of these S-acylations are suggested. Significance: First demonstration of SLN S-acylation and of the intramembranous S-oleoylation of a membrane protein. Sarcolipin (SLN) is a regulatory peptide present in sarcoplasmic reticulum (SR) from skeletal muscle of animals. We find that native rabbit SLN is modified by a fatty acid anchor on Cys-9 with a palmitic acid in about 60% and, surprisingly, an oleic acid in the remaining 40%. SLN used for co-crystallization with SERCA1a (Winther, A. M., Bublitz, M., Karlsen, J. L., Moller, J. V., Hansen, J. B., Nissen, P., and Buch-Pedersen, M. J. (2013) Nature 495, 265-2691; Ref. 1) is also palmitoylated/oleoylated, but is not visible in crystal structures, probably due to disorder. Treatment with 1 m hydroxylamine for 1 h removes the fatty acids from a majority of the SLN pool. This treatment did not modify the SERCA1a affinity for Ca2+ but increased the Ca2+-dependent ATPase activity of SR membranes indicating that the S-acylation of SLN or of other proteins is required for this effect on SERCA1a. Pig SLN is also fully palmitoylated/oleoylated on its Cys-9 residue, but in a reverse ratio of about 40/60. An alignment of 67 SLN sequences from the protein databases shows that 19 of them contain a cysteine and the rest a phenylalanine at position 9. Based on a cladogram, we postulate that the mutation from phenylalanine to cysteine in some species is the result of an evolutionary convergence. We suggest that, besides phosphorylation, S-acylation/deacylation also regulates SLN activity.
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