Chaperone code
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The Chaperone code refers to modifications of molecular chaperones that control protein folding. While the genetic code specifies how DNA makes proteins, while the histone code rules genomic transactions, the chaperone code controls how proteins are folded to produce a functional proteome.[1][2]
The chaperone code refers to the combinatorial array of post-translational modifications (enzymes add chemical modifications to amino acids that change their properties) - i.e. phosphorylation, acetylation, ubiquitination, methylation, etc - that are added to molecular chaperones to modulate their activity. Molecular chaperones are proteins specialized in folding and unfolding of the other cellular proteins, and the assembly and dismantling of protein complexes. This is critical in the regulation of protein-protein interactions and many cellular functions.
The chaperone code concept posits that combinations of posttranslational modifications at the surface of chaperones, including phosphorylation, acetylation[1], methylation,[3] ubiquitination,[4] control protein folding/unfolding and protein complex assembly/disassembly by regulation of substrate specificity, activity, subcellular localization and co-factor binding. [5][6] Because posttranslational modifications are marks that can be added and removed rapidly, they provide an efficient mechanism to explain the plasticity observed in proteome organization during cell growth and development.
Phosphorylation
Phosphorylation of chaperone proteins can affect their activity. HSP70, a major chaperone protein, was identified in 2012 as a hotspot of phospho-regulation. [7] Subsequently, phosphorylation of chaperone protein HSP70 by a cyclin dependent kinase was shown to be delay cell cycle progression in yeast and mammals by altering Cyclin D1 stability (a key regulator of the cell cycle). [8]
References
- ^ a b Nitika; Porter, Corey M.; Truman, Andrew W.; Truttmann, Matthias C. (2020-07-31). "Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code". The Journal of Biological Chemistry. 295 (31): 10689–10708. doi:10.1074/jbc.REV120.011666. ISSN 0021-9258. PMC 7397107. PMID 32518165.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Backe, Sarah J.; Sager, Rebecca A.; Woodford, Mark R.; Makedon, Alan M.; Mollapour, Mehdi (2020-08-07). "Post-translational modifications of Hsp90 and translating the chaperone code". The Journal of Biological Chemistry. 295 (32): 11099–11117. doi:10.1074/jbc.REV120.011833. ISSN 0021-9258. PMC 7415980. PMID 32527727.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Jakobsson, Magnus E.; Moen, Anders; Bousset, Luc; Egge-Jacobsen, Wolfgang; Kernstock, Stefan; Melki, Ronald; Falnes, Pål Ø. (2013-09-27). "Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation". The Journal of Biological Chemistry. 288 (39): 27752–27763. doi:10.1074/jbc.M113.483248. ISSN 0021-9258. PMC 3784692. PMID 23921388.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Kampinga, Harm H.; Craig, Elizabeth A. (August 2010). "The Hsp70 chaperone machinery: J-proteins as drivers of functional specificity". Nature reviews. Molecular cell biology. 11 (8): 579–592. doi:10.1038/nrm2941. ISSN 1471-0072. PMC 3003299. PMID 20651708.
- ^ Cloutier, Philippe; Coulombe, Benoit (2013). "Regulation of molecular chaperones through post-translational modifications: Decrypting the chaperone code". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1829 (5): 443–54. doi:10.1016/j.bbagrm.2013.02.010. PMC 4492711. PMID 23459247.
- ^ Cloutier, Philippe; Lavallée-Adam, Mathieu; Faubert, Denis; Blanchette, Mathieu; Coulombe, Benoit (2013). "A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity". PLOS Genetics. 9 (1): e1003210. doi:10.1371/journal.pgen.1003210. PMC 3547847. PMID 23349634.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Beltrao, Pedro; Albanèse, Véronique; Kenner, Lillian R.; Swaney, Danielle L.; Burlingame, Alma; Villén, Judit; Lim, Wendell A.; Fraser, James S.; Frydman, Judith; Krogan, Nevan J. (2012-07-20). "Systematic Functional Prioritization of Protein Posttranslational Modifications". Cell. 150 (2): 413–425. doi:10.1016/j.cell.2012.05.036. ISSN 0092-8674. PMID 22817900.
- ^ Truman, Andrew W.; Kristjansdottir, Kolbrun; Wolfgeher, Donald; Hasin, Naushaba; Polier, Sigrun; Zhang, Hong; Perrett, Sarah; Prodromou, Chrisostomos; Jones, Gary W.; Kron, Stephen J. (2012-12-07). "CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression". Cell. 151 (6): 1308–1318. doi:10.1016/j.cell.2012.10.051. ISSN 0092-8674. PMC 3778871. PMID 23217712.
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