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 posttranslational modifications - i.e. phosphorylation, acetylation, ubiquitination, methylation, etc - that target molecular chaperones to modulate their activity. Molecular chaperones are proteins specialized in folding and unfolding of the other cellular proteins and assembly and dismantling of protein complexes, thereby orchestrating the dynamic organization of the proteome. As a consequence, a limited number of chaperones must be able to act on a very large number of substrates in a highly regulated manner.
The chaperone code concept posits that combinations of posttranslational modifications at the surface of chaperones, including phosphorylation, acetylation, methylation, ubiquitination, etc, control protein folding/unfolding and protein complex assembly/disassembly by stipulating substrate specificity, activity, subcellular localization and co-factor binding. This conclusion emerges from the analysis of nearly two hundred reports in the literature,[3] including a key article published in 2013 reporting on the discovery of a novel family of methyltransferases that preferentially target and regulate molecular chaperones.[4] 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.
A large number of diseases, including degenerative neuromuscular disorders and cancer, are associated with dysfunction of molecular chaperones.
References
- ^ 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) - ^ 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)