Editing Chaperone (protein) (section)

== Nomenclature and examples of chaperone families ==
There are many different families of chaperones; each family acts to aid protein folding in a different way. In bacteria like ''[[Escherichia coli|E. coli]]'', many of these proteins are highly expressed under conditions of high stress, for example, when the bacterium is placed in high temperatures, thus heat shock protein chaperones are the most extensive.

A variety of nomenclatures are in use for chaperones. As heat shock proteins, the names are classically formed by "Hsp" followed by the approximate molecular mass in [[kilodalton]]s; such names are commonly used for eukaryotes such as yeast. The bacterial names have more varied forms, and refer directly to their apparent function at discovery. For example, "GroEL" originally stands for "phage growth defect, overcome by mutation in phage gene E, large subunit".<ref>{{cite journal |last1=Smith |first1=Tracy |title=The discovery of chaperonins |journal=Nature Structural Biology |date=1 December 1999 |volume=6 |issue=12 |pages=1090 |doi=10.1038/70015|pmid=10581544 |s2cid=6158370 |doi-access=free }}</ref>

=== Hsp10 and Hsp60 ===
{{main|HSP60}}
'''Hsp10/60''' (GroEL/GroES complex in ''E. coli'') is the best characterized large (~ 1 MDa) chaperone complex. [[GroEL]] (Hsp60) is a double-ring 14mer with a [[hydrophobic]] patch at its opening; it is so large it can accommodate native folding of 54-kDa [[Green fluorescent protein|GFP]] in its lumen. [[GroES]] (Hsp10) is a single-ring heptamer that binds to GroEL in the presence of ATP or ADP. GroEL/GroES may not be able to undo previous aggregation, but it does compete in the pathway of misfolding and aggregation.<ref>{{cite journal | vauthors = Fenton WA, Horwich AL | s2cid = 10328521 | title = Chaperonin-mediated protein folding: fate of substrate polypeptide | journal = Quarterly Reviews of Biophysics | volume = 36 | issue = 2 | pages = 229–56 | date = May 2003 | pmid = 14686103 | doi = 10.1017/S0033583503003883 }}</ref> Also acts in the [[Matrix (biology)|mitochondrial matrix]] as a molecular chaperone.

===Hsp70 and Hsp40===
{{main|Hsp70}}
[[File:Hsp70pocket.png|thumb|hsp70 pocket for substrate binding]]
'''Hsp70''' (DnaK in ''E. coli'') is perhaps the best characterized small (~ 70 kDa) chaperone. The [[Hsp70]] proteins are aided by Hsp40 proteins (DnaJ in ''E. coli''), which increase the ATP consumption rate and activity of the Hsp70s. The two proteins are named "Dna" in bacteria because they were initially identified as being required for ''E. coli'' DNA replication.<ref>{{cite journal |last1=Yochem |first1=J |last2=Uchida |first2=H |last3=Sunshine |first3=M |last4=Saito |first4=H |last5=Georgopoulos |first5=CP |last6=Feiss |first6=M |title=Genetic analysis of two genes, dnaJ and dnaK, necessary for Escherichia coli and bacteriophage lambda DNA replication. |journal=Molecular & General Genetics |date=4 August 1978 |volume=164 |issue=1 |pages=9–14 |doi=10.1007/BF00267593 |pmid=360041|s2cid=28144214 }}</ref>

It has been noted that increased expression of Hsp70 proteins in the cell results in a decreased tendency toward [[apoptosis]]. Although a precise mechanistic understanding has yet to be determined, it is known that Hsp70s have a high-affinity bound state to unfolded proteins when bound to [[Adenosine diphosphate|ADP]], and a low-affinity state when bound to [[Adenosine triphosphate|ATP]].

It is thought that many Hsp70s crowd around an unfolded substrate, stabilizing it and preventing aggregation until the unfolded molecule folds properly, at which time the Hsp70s lose affinity for the molecule and diffuse away.<ref>{{cite journal | vauthors = Mayer MP, Bukau B | title = Hsp70 chaperones: cellular functions and molecular mechanism | journal = Cellular and Molecular Life Sciences | volume = 62 | issue = 6 | pages = 670–84 | date = March 2005 | pmid = 15770419 | pmc = 2773841 | doi = 10.1007/s00018-004-4464-6 }}</ref> Hsp70 also acts as a mitochondrial and chloroplastic molecular chaperone in eukaryotes.

=== Hsp90 ===
{{main|Hsp90}}
'''Hsp90''' (HtpG in ''E. coli''{{efn|Initially identified as ''Drosophilia'' Hsp83 homologue. Name stands for "high temperature protein G".}}) may be the least understood chaperone. Its molecular weight is about 90 kDa, and it is necessary for viability in eukaryotes (possibly for prokaryotes as well). Heat shock protein 90 (Hsp90) is a molecular chaperone essential for activating many signaling proteins in the eukaryotic cell.

Each Hsp90 has an ATP-binding domain, a middle [[Protein domain|domain]], and a [[protein dimer|dimerization]] domain. Originally thought to clamp onto their substrate protein (also known as a client protein) upon binding ATP, the recently published structures by Vaughan ''et al.'' and Ali ''et al.'' indicate that client proteins may bind externally to both the N-terminal and middle domains of Hsp90.<ref>{{cite journal | vauthors = Vaughan CK, Gohlke U, Sobott F, Good VM, Ali MM, Prodromou C, Robinson CV, Saibil HR, Pearl LH | display-authors = 6 | title = Structure of an Hsp90-Cdc37-Cdk4 complex | journal = Molecular Cell | volume = 23 | issue = 5 | pages = 697–707 | date = September 2006 | pmid = 16949366 | pmc = 5704897 | doi = 10.1016/j.molcel.2006.07.016 }}</ref><ref>{{cite journal | vauthors = Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH | display-authors = 6 | title = Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex | journal = Nature | volume = 440 | issue = 7087 | pages = 1013–7 | date = April 2006 | pmid = 16625188 | pmc = 5703407 | doi = 10.1038/nature04716 | bibcode = 2006Natur.440.1013A }}</ref>

Hsp90 may also require [[co-chaperone]]s-like [[immunophilin]]s, [[STIP1|Sti1]], p50 ([[Cdc37]]), and [[Aha1]], and also cooperates with the Hsp70 chaperone system.<ref>{{cite journal | vauthors = Terasawa K, Minami M, Minami Y | title = Constantly updated knowledge of Hsp90 | journal = Journal of Biochemistry | volume = 137 | issue = 4 | pages = 443–7 | date = April 2005 | pmid = 15858167 | doi = 10.1093/jb/mvi056 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Pearl LH, Prodromou C | title = Structure and mechanism of the Hsp90 molecular chaperone machinery | journal = Annual Review of Biochemistry | volume = 75 | pages = 271–94 | year = 2006 | pmid = 16756493 | doi = 10.1146/annurev.biochem.75.103004.142738 }}</ref>

=== Hsp100 ===
{{main|HSP100}}
'''Hsp100''' (Clp family in ''E. coli'') proteins have been studied ''[[in vivo]]'' and ''[[in vitro]]'' for their ability to target and unfold tagged and misfolded proteins.

Proteins in the Hsp100/Clp family form large [[Quaternary structure#Nomenclature of quaternary structures|hexameric]] structures with unfoldase activity in the presence of ATP. These proteins are thought to function as chaperones by processively threading client proteins through a small 20 Å (2 [[nanometer|nm]]) pore, thereby giving each client protein a second chance to fold.

Some of these Hsp100 chaperones, like ClpA and ClpX, associate with the double-ringed [[Quaternary structure#Nomenclature of quaternary structures|tetradecameric]] [[serine protease]] ClpP; instead of catalyzing the refolding of client proteins, these complexes are responsible for the targeted destruction of tagged and misfolded proteins.

[[Hsp104]], the Hsp100 of [[Saccharomyces cerevisiae]], is essential for the propagation of many [[yeast prions]]. Deletion of the HSP104 gene results in cells that are unable to propagate certain [[prions]].