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The '''chaperone code''' refers to [[Post-translational modification|post-translational modifications]] of molecular [[Chaperone (protein)|chaperones]] that control protein folding. Whilst the [[genetic code]] specifies how [[DNA]] makes proteins, and the [[histone code]] regulates histone-DNA interactions, the chaperone code controls how proteins are folded to produce a functional [[proteome]].<ref name=":0">{{Cite journal|last1=Nitika|last2=Porter|first2=Corey M.|last3=Truman|first3=Andrew W.|last4=Truttmann|first4=Matthias C.|date=2020-07-31|title=Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code|journal=The Journal of Biological Chemistry|volume=295|issue=31|pages=10689–10708|doi=10.1074/jbc.REV120.011666|issn=0021-9258|pmc=7397107|pmid=32518165}}</ref><ref name=":1">{{Cite journal|last1=Backe|first1=Sarah J.|last2=Sager|first2=Rebecca A.|last3=Woodford|first3=Mark R.|last4=Makedon|first4=Alan M.|last5=Mollapour|first5=Mehdi|date=2020-08-07|title=Post-translational modifications of Hsp90 and translating the chaperone code|journal=The Journal of Biological Chemistry|volume=295|issue=32|pages=11099–11117|doi=10.1074/jbc.REV120.011833|issn=0021-9258|pmc=7415980|pmid=32527727}}</ref>
The chaperone code refers to the combinatorial array of [[Post-translational modification|post-translational modifications]] (enzymes add chemical modifications to amino acids that change their properties) —i.e. [[phosphorylation]], [[acetylation]], [[Ubiquitin|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. Because post-translational 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.
The chaperone code concept posits that combinations of
1) [[Substrate (chemistry)|chaperone-substrate]] affinity and specificity
2) chaperone ATPase and therefore its refolding activity
3) chaperone localization
4) chaperone-co-chaperone interaction <ref>{{cite journal |doi=10.1016/j.bbagrm.2013.02.010 |pmid=23459247 |pmc=4492711 |title=Regulation of molecular chaperones through post-translational modifications: Decrypting the chaperone code |journal=Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |volume=1829 |issue=5 |pages=443–54 |year=2013 |last1=Cloutier |first1=Philippe |last2=Coulombe |first2=Benoit }}</ref><ref>{{cite journal |doi=10.1371/journal.pgen.1003210 |pmid=23349634 |pmc=3547847 |title=A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity |journal=PLOS Genetics |volume=9 |issue=1 |pages=e1003210 |year=2013 |last1=Cloutier |first1=Philippe |last2=Lavallée-Adam |first2=Mathieu |last3=Faubert |first3=Denis |last4=Blanchette |first4=Mathieu |last5=Coulombe |first5=Benoit }}</ref> .
== Levels of the Chaperone Code ==
The Chaperone code is incredibly complex with multiple layers of potential regulation. Studies of the chaperone code may include:
Level 1: Understanding the role and regulation of single PTMs on a single chaperone
Level 2: Cross-talk of different PTMs on a single amino acid or between PTMs on different amino acids (on a single chaperone)
Level 3: Understanding of why chaperone paralogs have different PTMs
Level 4: Cross-talk of PTMs between different chaperones i.e. between Hsp90 and Hsp70
Level 5: Understanding the role and regulation of single PTMs on a single co-chaperone molecule
Level 6: Understanding the entire chaperone code-all the PTMs on all major chaperones, co-chaperones that control all aspects of life.
▲The chaperone code concept posits that combinations of posttranslational modifications at the surface of chaperones, including phosphorylation, acetylation<ref name=":0" />, methylation,<ref>{{Cite journal|last1=Jakobsson|first1=Magnus E.|last2=Moen|first2=Anders|last3=Bousset|first3=Luc|last4=Egge-Jacobsen|first4=Wolfgang|last5=Kernstock|first5=Stefan|last6=Melki|first6=Ronald|last7=Falnes|first7=Pål Ø.|date=2013-09-27|title=Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation|journal=The Journal of Biological Chemistry|volume=288|issue=39|pages=27752–27763|doi=10.1074/jbc.M113.483248|issn=0021-9258|pmc=3784692|pmid=23921388}}</ref> ubiquitination,<ref>{{Cite journal|last1=Kampinga|first1=Harm H.|last2=Craig|first2=Elizabeth A.|date=August 2010|title=The Hsp70 chaperone machinery: J-proteins as drivers of functional specificity|journal=Nature Reviews. Molecular Cell Biology|volume=11|issue=8|pages=579–592|doi=10.1038/nrm2941|issn=1471-0072|pmc=3003299|pmid=20651708}}</ref> control protein folding/unfolding and protein complex assembly/disassembly by regulation of [[Substrate (chemistry)|substrate]] specificity, activity, subcellular localization and co-factor binding.<ref>{{cite journal |doi=10.1016/j.bbagrm.2013.02.010 |pmid=23459247 |pmc=4492711 |title=Regulation of molecular chaperones through post-translational modifications: Decrypting the chaperone code |journal=Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |volume=1829 |issue=5 |pages=443–54 |year=2013 |last1=Cloutier |first1=Philippe |last2=Coulombe |first2=Benoit }}</ref><ref>{{cite journal |doi=10.1371/journal.pgen.1003210 |pmid=23349634 |pmc=3547847 |title=A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity |journal=PLOS Genetics |volume=9 |issue=1 |pages=e1003210 |year=2013 |last1=Cloutier |first1=Philippe |last2=Lavallée-Adam |first2=Mathieu |last3=Faubert |first3=Denis |last4=Blanchette |first4=Mathieu |last5=Coulombe |first5=Benoit }}</ref> 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 ==
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