Chaperones are proteins that are involved in the non-covalent folding and unfolding of other macromolecules. It exists both in prokaryotes and eukaryotes. Some chaperones are constitutively expressed in the system however, there are other chaperones that are expressed only in response to an external stimulus or stress such as heat and therefore they are referred to as ''heat shock proteins''.They are classified based on their structure, size, molecular weight and function in to several classes such as Hsp100, Hsp90, Hsp60 [[Chaperonin]], small heat shock proteins (alpha)-crystallin proteins. They do not undergo denaturation themselves when exposed to stress because of better hydrogen bonding, strong hydrophobic core interactions, enhanced secondary structure and helix dipole stabilization.
Chaperones are proteins that are involved in the non-covalent folding and unfolding of other macromolecules. It exists both in prokaryotes and eukaryotes. Some chaperones are constitutively expressed in the system however, there are other chaperones that are expressed only in response to an external stimulus or stress such as heat and therefore they are referred to as ''heat shock proteins''.They are classified based on their structure, size, molecular weight and function in to several classes such as Hsp100, Hsp90, Hsp60 [[Chaperonin]], small heat shock proteins (alpha)-crystallin proteins. They do not undergo denaturation themselves when exposed to stress because of better hydrogen bonding, strong hydrophobic core interactions, enhanced secondary structure and helix dipole stabilization.
Chaperones are proteins that are involved in the non-covalent folding and unfolding of other macromolecules. It exists both in prokaryotes and eukaryotes. Some chaperones are constitutively expressed in the system however, there are other chaperones that are expressed only in response to an external stimulus or stress such as heat and therefore they are referred to as heat shock proteins.They are classified based on their structure, size, molecular weight and function in to several classes such as Hsp100, Hsp90, Hsp60 Chaperonin, small heat shock proteins (alpha)-crystallin proteins. They do not undergo denaturation themselves when exposed to stress because of better hydrogen bonding, strong hydrophobic core interactions, enhanced secondary structure and helix dipole stabilization.
Chaperones bind to the newly synthesized proteins helping them acquire their properly folded 3D structure [1] Besides, chaperones help in targeting the native proteins to their respective organelles [2][3] The first identified chaperones were the histone chaperones that are continously involved in histone metabolism thus regulating genome function, stability and identity[4]. Many protozoan parasites such as Plasmodium falciparum requires these proteins for cytoprotection [5][6]Chaperones actively participate in the maintenance of proteome integrity, and protein homeostasis (proteostasis) which requires a syncrhonization in various chaperones tuning the process [7].
Disease
Chaperones are instrumental in protein folding processes. Any alteration in this process leads to protein aggregation and formation of inclusion bodies. Protein misfolding results in various diseases such as Alzheimer[8],Cytosolic neurofibrillatory tangles,Parkinson[9],Familial amyotrophic lateral sclerosis, Huntington, Spinocerebellar ataxia 1, 2, 3, disease, Spinobulbar muscular atrophy and ageing[10].
Relevance
Modulation of chaperones expression is the new therapeutic approach for neurodegenerative and other disease arising from protein misfolding. There is a distinct network of chaperones and co chaperones that either directly influences the substrate proteins or in association with the protein degradation pathways such as the ubiquitin-proteasome-system or autophagy, results in the removal of completely misfolded and pathogenic proteins[11].
Structural highlights
Structurally, heat shock proteins have a N-terminal ATPase domain followed by a substrate binding domain with elongated C-terminal. These domains allosterically regulate the hsp70 functioning. 4JN4 is a representative example of a chaperone system in complex with ADP.
↑Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R. A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature. 1988 Apr 28;332(6167):800-5. PMID:3282178 doi:https://dx.doi.org/10.1038/332800a0
↑Halperin L, Jung J, Michalak M. The many functions of the endoplasmic reticulum chaperones and folding enzymes. IUBMB Life. 2014 May 19. doi: 10.1002/iub.1272. PMID:24839203 doi:https://dx.doi.org/10.1002/iub.1272
↑Gurard-Levin ZA, Quivy JP, Almouzni G. Histone chaperones: assisting histone traffic and nucleosome dynamics. Annu Rev Biochem. 2014 Jun 2;83:487-517. doi:, 10.1146/annurev-biochem-060713-035536. PMID:24905786 doi:https://dx.doi.org/10.1146/annurev-biochem-060713-035536
↑Matambo TS, Odunuga OO, Boshoff A, Blatch GL. Overproduction, purification, and characterization of the Plasmodium falciparum heat shock protein 70. Protein Expr Purif. 2004 Feb;33(2):214-22. PMID:14711509
↑Misra G, Ramachandran R. Hsp70-1 from Plasmodium falciparum: protein stability, domain analysis and chaperone activity. Biophys Chem. 2009 Jun;142(1-3):55-64. doi: 10.1016/j.bpc.2009.03.006. Epub 2009 , Mar 16. PMID:19339102 doi:https://dx.doi.org/10.1016/j.bpc.2009.03.006
↑Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Hartl FU. Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem. 2013;82:323-55. doi: 10.1146/annurev-biochem-060208-092442. PMID:23746257 doi:https://dx.doi.org/10.1146/annurev-biochem-060208-092442
↑Ebrahimi-Fakhari D, Saidi LJ, Wahlster L. Molecular chaperones and protein folding as therapeutic targets in Parkinson's disease and other synucleinopathies. Acta Neuropathol Commun. 2013 Dec 5;1(1):79. doi: 10.1186/2051-5960-1-79. PMID:24314025 doi:https://dx.doi.org/10.1186/2051-5960-1-79
References
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