Chaperones: Difference between revisions

Chaperones are proteins that are involved in the folding and unfolding of other macromolecules. The word chaperone means 'giving protection' which implies the idea of preventing new proteins from misfolding. They exists both in prokaryotes and eukaryotes. Some chaperones are constitutively expressed in the system where as other chaperones 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 [[Hsp40s]], Hsp60s [[Chaperonin]], Hsp70s, Hsp90s such as [[1am1]], [[Hsp100s]] and small heat shock proteins like (alpha)-crystallin proteins. Various classes of molecular chaperones cooperate for the folding of the nascent polypeptide chains in the cyotplasm <ref>doi: 10.1146/annurev-biochem-060208-092442</ref>.  

Chaperones bind to the newly synthesized and unfolded proteins helping them acquire their properly folded 3D structure <ref>PMID: 3112578</ref>. Besides, chaperones help in targeting the native proteins to their respective organelles <ref>PMID:3282178</ref><ref>DOI: 10.1002/iub.1272</ref>. The first identified chaperones were the histone chaperones that are continously involved in histone metabolism thus regulating genome function, stability and identity<ref>doi: 10.1146/annurev-biochem-060713-035536</ref>. Many protozoan parasites such as ''Plasmodium falciparum'' requires these proteins for cytoprotection <ref>PMID: 14711509</ref> <ref>PMID: 19339102</ref>. Chaperones actively participate in the maintenance of proteome integrity and protein homeostasis (proteostasis) which requires a syncrhonization in various chaperone's tuning the process <ref>DOI: 10.1146/annurev-biochem-060208-092442</ref>.

Chaperones are instrumental in protein folding processes. Alteration in this process may lead to protein aggregation and formation of inclusion bodies. Protein misfolding may result in various diseases such as Alzheimer <ref>PMID:16048838</ref>, Parkinson <ref>PMID:16610362</ref>, Familial amyotrophic lateral sclerosis  <ref>doi:10.1002/prca.200780023</ref>, Huntington<ref>PMID:24323530</ref, Spinocerebellar ataxia 1, 2, 3 <ref>doi:10.1016/B978-0-444-51892-7.00027-9</ref>, Spinobulbar muscular atrophy <ref>doi: 10.1093/hmg/11.5.515</ref> and ageing <ref>doi:10.1111/j.1742-4658.2006.05181.x</ref>.

Structurally, Hsp70 have a N-terminal <scene name='59/591341/Atpase_domain/2'>ATPase domain</scene> followed by a <scene name='59/591341/Substrate_binding_domain/1'>substrate binding domain with elongated C-terminal</scene>. These domains <scene name='59/591341/Transition1/2'>allosterically regulate</scene> the hsp70 functioning. <scene name='59/591341/4jn4/2'>4JN4</scene> is a representative example of a chaperone system in complex with ADP. In the 2D figure given below, panel A indicates the various folded (green) and unfolded (red)regions in Hsp70. Panel B shows the structural organization of Hsp 70 indicating its various domains. ATP binding and hydrolysis regulates the affinity for substrate proteins which thereafter enhances ATP hydrolysis.

[[Image:1-s2.0-S0301462209000520-gr1.jpg|left|500px|thumb|Structural organization of Hsp70]]