Palmitation is the covalent attachment of a residue of one of the higher fatty acids to a protein with the formation of a thioether bond . Most often, palmitic acid is added (hence the name) to a sulfur- containing amino acid , most often cysteine , less often to serine or threonine . Usually, membrane proteins, such as surface receptor molecules, undergo palmitation. [1] The role of palmitation in changing the functionality of a protein depends on the specific protein.
Palmitation increases the hydrophobicity of proteins and contributes to their localization in the lipid bilayer of the cell membrane. Also, palmitation appears to play a significant role in facilitating the intracellular transport of proteins between the cell membrane compartments. [2] as well as in modulating protein-protein interactions. [3] Unlike prenylation and myristoylation, palmitation is usually reversible, since the bond between the palmitic acid residue and the protein is most often thioester. The reverse reaction of depalmitation is catalyzed by palmitoyl protein thioesterase. Since palmitation is a dynamic process of posttranslational modification , it is considered that it plays a role in the localization of proteins, in changing the nature of protein-protein interactions, or in regulating the ability of proteins to bind to certain ligands or on the ability of proteins to heteropolymerization.
An example of a protein that is subjected to palmitation is hemagglutinin , a membrane glycoprotein that is used by the influenza virus to attach to the surface receptors of the host cell and initiate the process of penetration into it. [4] In recent years, palmitoylation of a number of enzymes and receptors , such as the G-protein , 5-HT1A receptor , endothelial synthase nitric oxide , has been described. Another well-known example is an important Wnt signaling protein that is modified by palmitoleic acid attached to a serine residue. This is an unusual type of O- acylation , which is mediated by a membrane-bound O-acyltransferase. [5] When transmitting a signal through G-proteins, palmitation of the α-subunit, prenylation of the γ-subunit and myristoylation in several subunits lead to the fact that the G-protein is “anchored” on the inner side of the cell membrane, which creates conditions for its interaction with G-protein-bound receptors. [6]
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The role of palmitation in the regulation of synaptic plasticity
Scientists have appreciated the importance of attaching long hydrophobic chains to a certain signal cell protein. A good illustration of the importance of this phenomenon is the distribution of proteins in the synapse. One of the main proteins responsible for this process is the postsynaptic compaction protein (95 kDa) ( postsynaptic density protein 95 or PSD-95 ). In the palmitated state, it remains bound to the membrane . Such a connection allows it to interact with ion channels and organize them into a cluster on the postsynaptic membrane. Also, in the presynaptic neuron, the palmitation of the SNAP-25 protein allows the SNARE complex to dissociate during endocytosis . Thus, palmitation is involved in the regulation of neurotransmitter secretion. [7]
Palmitation of delta catenin seems to coordinate the changes stimulated by neuronal activity in the adhesion of synaptic molecules, the synaptic structure and localization of receptors that are involved in the formation of memory . [eight]
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See also
- Myristoylation
- Prenealing
Notes
- Inder Linder, ME, " Protective Lipidation , F. Tamanoi and DS Sigman, eds., Pp. Reversible modification of proteins with thioester-linked fatty acids," 215-40 (San Diego, CA: Academic Press, 2000).
- ↑ Rocks, O., Peyker, A., Kahms, M., Verveer, PJ, Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., Bastiaens, Rit isoforms ( English) // Science: journal. - 2005. - Vol. 307 , no. 5716 . - P. 1746-1752 . - DOI : 10.1126 / science.1105654 . - PMID 15705808 .
- ↑ Basu, J., "Protein palmitoylation and dynamic modulation of protein function," Current Science , Vol. 87, No. 2, pp. 212-17 (25 July 2004), http://www.ias.ac.in/currsci/jul252004/contents.htm
- ↑ influenza viruses, the encyclopedia of virology, http://www.sciencedirect.com/science ? = 10 & _acct = C000011279 & _version = 1 & _urlVersion = 0 & _userid = 5399531 & md5 = 607bbb1a7d18138457365550b9471eb5 .
- ↑ Takada R., Satomi Y., Kurata T., Ueno N., Norioka S., Kondoh H., Takao T., Takada S. Monoensaturation of Wnt secretion (English) / / Dev Cell : journal. - 2006. - Vol. 11 , no. 6 - P. 791-801 . - DOI : 10.1016 / j.devcel.2006.10.003 . - PMID 17141155 .
- ↑ Wall, MA; Coleman, DE; Lee, E; Iñiguez-Lluhi, JA; Posner, BA; Gilman, AG; Sprang, SR The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. (eng.) // Cell : journal. - Cell Press , 1995. - 15 December ( vol. 83 , no. 6 ). - P. 1047-1058 . - DOI : 10.1016 / 0092-8674 (95) 90220-1 . - PMID 8521505 .
- “Molecular Mechanisms of Synaptogenesis.” Edited by Alexander Dityatev and Alaa El-Husseini. Springer: New York, NY. 2006. pg. 72-75
- ↑ Brigidi GS, Sun Y., Beccano-Kelly D., Pitman K., Jobasser M., Borgland S. L., Milnerwood A. J., Bamji S X. Palmitoylation of [delta] -catenin by DHHC5 mediates activity-induced synapse plasticity (English) // Nature Neuroscience : journal. - 2014. - 23 January. - DOI : 10.1038 / nn.3657 .
- Smotrys J., Linder A. Palmitoylation of Intrallular Signaling Proteins: Regulation and Function (Eng.) // Annu Rev Biochem : journal. - 2004. - Vol. 73 . - P. 559-587 . - DOI : 10.1146 / annurev.biochem.73.011303.073954 . - PMID 15189153 .
- Resh, M. (2006) “Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules” . Sci STK. 359 October 31.
- Linder M., Deschenes R. Palmitoylation: policing protein stability and traffic (English) // Nature: journal. - 2007. - Vol. 8 - P. 74-84 . - DOI : 10.1038 / nrm2084 .