View source for Chaperonin

{{Short description|Family of heat shock proteins}}
{{About|the protein family|the human mitochondrial protein|HSPD1}}
{{Infobox protein family
| Symbol = Cpn60_TCP1 
| Name = TCP-1/Cpn60 chaperonin family 
| image = PDB 1grl EBI.jpg
| width = 
| caption = Structure of the bacterial chaperonin [[GroEL]].<ref name="pmid7935790">{{cite journal | vauthors = Braig K, Otwinowski Z, Hegde R, Boisvert DC, Joachimiak A, Horwich AL, Sigler PB | title = The crystal structure of the bacterial chaperonin GroEL at 2.8 A | journal = Nature | volume = 371 | issue = 6498 | pages = 578–86 | date = October 1994 | pmid = 7935790 | doi = 10.1038/371578a0 | bibcode = 1994Natur.371..578B | s2cid = 4341993 }}</ref>
| Pfam= PF00118
| InterPro= IPR002423
| SMART= 
| Prosite = PDOC00610
| SCOP = 1grl
|CATH=5GW5
| TCDB = 
| OPM family= 
| OPM protein= 
| PDB= 
{{PDB3|1sx3}}K:23-525    {{PDB3|1kpo}}Z:23-525    {{PDB3|1fya}}A:190-375   
{{PDB3|1gru}}H:23-525    {{PDB3|1xck}}F:23-525    {{PDB3|1kp8}}E:23-525    
{{PDB3|1pcq}}J:23-524    {{PDB3|1aon}}J:23-524    {{PDB3|1mnf}}I:23-525    
{{PDB3|1svt}}J:23-524    {{PDB3|2c7d}}K:23-525    {{PDB3|1dkd}}C:190-335   
{{PDB3|1j4z}}L:23-525    {{PDB3|1oel}}E:23-524    {{PDB3|2c7c}}H:23-525    
{{PDB3|1gr5}}H:23-525    {{PDB3|1sx4}}E:23-524    {{PDB3|1kid}} :190-375   
{{PDB3|1gr6}}F:23-525    {{PDB3|1ss8}}B:23-524    {{PDB3|1fy9}}A:190-375   
{{PDB3|1dk7}}A:190-335   {{PDB3|1jon}} :190-335   {{PDB3|1la1}}A:187-378   
{{PDB3|1iok}}A:23-526    {{PDB3|1wf4}}e:22-526    {{PDB3|1we3}}E:22-526    
{{PDB3|1sjp}}B:42-522    {{PDB3|1srv}}A:1-143     {{PDB3|1a6d}}B:33-521    
{{PDB3|1a6e}}B:33-521    {{PDB3|1e0r}}B:215-366   {{PDB3|1ass}} :214-364   
{{PDB3|1asx}} :214-364   {{PDB3|1gn1}}H:210-380   {{PDB3|1gml}}B:210-380   
|CDD=cd00309
}}
'''Chaperonins''', abbreviated '''Cpn''', '''Cpn60''', or '''HSP60''', are a family of [[heat shock protein]]s  that assist in the [[protein folding|folding]] of newly synthesized proteins and refolding of misfolded proteins during stressful conditions such as high temperature. They are [[protein complex]]es consisting of about 16 protein subunits of ~60 [[Dalton (unit)|kDa]] each. Chaperonins belong to a large class of molecules and complexes that assist protein folding, called [[molecular chaperones]].<ref>{{Cite web |url=http://www.hhmi.org/research/investigators/horwich_bio.html |title=Howard Hughes Investigators: Arthur L. Horwich, M.D. |access-date=2011-09-12 |archive-date=2019-07-26 |archive-url=https://web.archive.org/web/20190726232130/https://www.hhmi.org/scientists/arthur-l-horwich }}</ref><ref name=":0">{{cite journal | vauthors = Conway de Macario E, Yohda M, Macario AJ, Robb FT | title = Bridging human chaperonopathies and microbial chaperonins | journal = Communications Biology | volume = 2 | issue = 1 | article-number = 103 | date = 2019-03-15 | pmid = 30911678 | pmc = 6420498 | doi = 10.1038/s42003-019-0318-5 }}</ref> 

Newly made proteins usually must [[protein folding|fold]] from a linear chain of amino acids into a three-dimensional [[protein tertiary structure|tertiary structure]]. The energy to fold proteins is supplied by non-covalent interactions between the amino acid side chains of each protein, and by solvent effects. Most proteins spontaneously fold into their most stable three-dimensional conformation, which is usually also their functional conformation, but occasionally proteins mis-fold.  Molecular chaperones catalyze protein refolding by accelerating partial unfolding of misfolded proteins, aided by energy supplied by the hydrolysis of [[adenosine triphosphate]] (ATP).  Chaperonin proteins may also tag misfolded proteins to be degraded.<ref name=":0"/>

== Structure ==
The structure of these chaperonins resemble two donuts stacked on top of one another to create a barrel. Each ring is composed of either 7, 8 or 9 subunits depending on the organism in which the chaperonin is found. Each ~60kDa peptide chain can be divided into three domains, apical, intermediate, and equatorial.<ref name="pmid29696145">{{cite journal | vauthors = Ansari MY, Mande SC | title = A Glimpse Into the Structure and Function of Atypical Type I Chaperonins | journal = Frontiers in Molecular Biosciences | volume = 5 | article-number = 31 | date = 2018 | pmid = 29696145 | doi = 10.3389/fmolb.2018.00031 | pmc = 5904260 | doi-access = free }}</ref>

The original chaperonin is proposed to have evolved from a [[peroxiredoxin]].<ref name=willison>{{cite journal |last1=Willison |first1=KR |title=The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its mechanism that folds actin into a protein spring. |journal=The Biochemical Journal |date=5 October 2018 |volume=475 |issue=19 |pages=3009–3034 |doi=10.1042/BCJ20170378 |pmid=30291170|hdl=10044/1/63924 |s2cid=52923821 |hdl-access=free }}</ref>

== Classification ==

===Group I===
[[File:GroES-GroEL.png|thumb|GroES/GroEL complex (side)]]
Group I chaperonins (Cpn60){{efn|The GroEL family is referred to, by InterPro, as Cpn60. However, CDD uses Cpn60 to refer to the Group II proteins in archaea.}} are found in [[bacteria]] as well as [[organelles]] of [[endosymbiotic]] origin: [[chloroplasts]] and [[mitochondria]].

The GroEL/GroES complex in ''[[E. coli]]'' is a Group I chaperonin and the best characterized large (~ 1 MDa) chaperonin complex. 
* [[GroEL]] is a double-ring 14mer with a greasy [[hydrophobic]] patch at its opening and can accommodate the native folding of substrates 15-60 kDa in size.
* [[GroES]] (is a single-ring heptamer that binds to GroEL in the presence of ATP or [[transition state]] analogues of ATP hydrolysis, such as ADP-AlF<sub>3</sub>. It is like a cover that covers GroEL (box/bottle).

GroEL/GroES may not be able to undo protein aggregates, but kinetically it competes in the pathway of misfolding and aggregation, thereby preventing aggregate formation.<ref name="pmid14686103">{{cite journal | vauthors = Fenton WA, Horwich AL | 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 | s2cid = 10328521 }}</ref>

The Cpn60 subfamily was discovered in 1988.<ref name="PUB00004022">{{cite journal | vauthors = Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ | display-authors = 6 | title = Homologous plant and bacterial proteins chaperone oligomeric protein assembly | journal = Nature | volume = 333 | issue = 6171 | pages = 330–4 | date = May 1988 | pmid = 2897629 | doi = 10.1038/333330a0 | bibcode = 1988Natur.333..330H | s2cid = 4325057 }}</ref> It was sequenced in 1992. The cpn10 and cpn60 oligomers also require Mg<sup>2+</sup>-ATP in order to interact to form a functional complex.<ref name="PUB00004550">{{cite journal | vauthors = Prasad TK, Stewart CR | title = cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin HSP60 and gene expression during seed germination and heat shock | journal = Plant Molecular Biology | volume = 18 | issue = 5 | pages = 873–85 | date = March 1992 | pmid = 1349837 | doi = 10.1007/BF00019202 | bibcode = 1992PMolB..18..873P | s2cid = 40768099 }}</ref> The binding of cpn10 to cpn60 inhibits the weak [[ATPase]] activity of cpn60.<ref name="PUB00002183">{{cite journal | vauthors = Schmidt A, Schiesswohl M, Völker U, Hecker M, Schumann W | title = Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis | journal = Journal of Bacteriology | volume = 174 | issue = 12 | pages = 3993–9 | date = June 1992 | pmid = 1350777 | pmc = 206108 | doi = 10.1128/jb.174.12.3993-3999.1992 }}</ref>

The [[RuBisCO]] subunit binding protein is a member of this family.<ref name="PUB00001725" /> The crystal structure of ''[[Escherichia coli]]'' GroEL has been resolved to 2.8 Å.<ref name="PUB00004190">{{cite journal | vauthors = Braig K, Otwinowski Z, Hegde R, Boisvert DC, Joachimiak A, Horwich AL, Sigler PB | title = The crystal structure of the bacterial chaperonin GroEL at 2.8 A | journal = Nature | volume = 371 | issue = 6498 | pages = 578–86 | date = October 1994 | pmid = 7935790 | doi = 10.1038/371578a0 | bibcode = 1994Natur.371..578B | s2cid = 4341993 }}</ref>

Some bacteria use multiple copies of this chaperonin, probably for different peptides.<ref name="pmid29696145"/>

===Group II===
[[File:PDB-5GW5-TRiC-AMP-PNP.png|thumbnail|Structure of ''Saccharomyces cerevisiae'' TRiC in the AMP-PNP bound state ({{PDB|5GW5}}).<ref name="Zang Jin Wang Cui pp. 1083–1091">{{cite journal | vauthors = Zang Y, Jin M, Wang H, Cui Z, Kong L, Liu C, Cong Y | title = Staggered ATP binding mechanism of eukaryotic chaperonin TRiC (CCT) revealed through high-resolution cryo-EM | journal = Nature Structural & Molecular Biology | volume = 23 | issue = 12 | pages = 1083–1091 | date = December 2016 | pmid = 27775711 | doi = 10.1038/nsmb.3309 | publisher = Springer Science and Business Media LLC | s2cid = 12001964 }}</ref>]]
Group II chaperonins (TCP-1), found in the [[eukaryotic]] [[cytosol]] and in [[archaea]], are more poorly characterized.

* The complex in archaea is called the [[thermosome]]. A homo-16mer in some archaea, it is regarded as the prototypical type II chaperonin.{{efn|Some archaeons have evolved to use, like eukaryotes, different subunits. ''Methanosarcina acetivorans'' is known to have five types of subunits.<ref name=":0"/> The ancestor to eukarotic TriC is thought to have two.<ref name="willison"/>}}
*  [[TRiC (complex)|TRiC]], the eukaryotic chaperonin, is composed of two rings of eight different though [[paralog|related subunit]]s, each thought to be represented once per eight-membered ring. TRiC was originally thought to fold only the cytoskeletal proteins actin and tubulin but is now known to fold dozens of substrates.

''[[Methanococcus maripaludis]]'' chaperonin (Mm cpn) is composed of sixteen identical subunits (eight per ring). It has been shown to fold the mitochondrial protein rhodanese; however, no natural substrates have yet been identified.<ref name="methanococcus">{{cite journal | vauthors = Kusmierczyk AR, Martin J | title = Nucleotide-dependent protein folding in the type II chaperonin from the mesophilic archaeon Methanococcus maripaludis | journal = The Biochemical Journal | volume = 371 | issue = Pt 3 | pages = 669–73 | date = May 2003 | pmid = 12628000 | pmc = 1223359 | doi = 10.1042/BJ20030230 }}</ref>

Group II chaperonins are not thought to utilize a GroES-type cofactor to fold their substrates.  They instead contain a "built-in" lid that closes in an ATP-dependent manner to encapsulate its substrates, a process that is required for optimal protein folding activity. They also interact with a co-chaperone, [[prefoldin]], that helps move the substrate in.<ref name=":0"/>

===Other families===
Group III includes some bacterial Cpns that are related to Group II. They have a lid, but the lid opening is noncooperative in them. They are thought to be an ancient relative of Group II.<ref name=":0" /><ref name="pmid29696145"/>

A Group I chaperonin gp146 from [[phage EL]] does not use a lid, and its donut interface is more similar to Group II. It might represent another ancient type of chaperonin.<ref>{{cite journal | vauthors = Bracher A, Paul SS, Wang H, Wischnewski N, Hartl FU, Hayer-Hartl M | title = Structure and conformational cycle of a bacteriophage-encoded chaperonin | journal = PLOS ONE | volume = 15 | issue = 4 | article-number = e0230090 | date = 27 April 2020 | pmid = 32339190 | doi = 10.1371/journal.pone.0230090 | pmc = 7185714 | bibcode = 2020PLoSO..1530090B | doi-access = free }}</ref>

== Mechanism of action ==
Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatic [[hydrolysis]] of ATP as well as binding of substrate proteins and cochaperonins, such as GroES. These conformational changes allow the chaperonin to bind an unfolded or misfolded protein, encapsulate that protein within one of the cavities formed by the two rings, and release the protein back into solution. Upon release, the substrate protein will either be folded or will require further rounds of folding, in which case it can again be bound by a chaperonin.

The exact mechanism by which chaperonins facilitate folding of substrate proteins is unknown. According to recent analyses by different experimental techniques, GroEL-bound substrate proteins populate an ensemble of compact and locally expanded states that lack stable tertiary interactions.<ref name="HartlHayer-Hartl2009">{{cite journal | vauthors = Hartl FU, Hayer-Hartl M | title = Converging concepts of protein folding in vitro and in vivo | journal = Nature Structural & Molecular Biology | volume = 16 | issue = 6 | pages = 574–81 | date = June 2009 | pmid = 19491934 | doi = 10.1038/nsmb.1591 | s2cid = 205522841 }}</ref> A number of models of chaperonin action have been proposed, which generally focus on two (not mutually exclusive) roles of chaperonin interior: passive and active. Passive models treat the chaperonin cage as an inert form, exerting influence by reducing the conformational space accessible to a protein substrate or preventing intermolecular interactions e.g. by aggregation prevention.<ref name="ApetriHorwich2008">{{cite journal | vauthors = Apetri AC, Horwich AL | title = Chaperonin chamber accelerates protein folding through passive action of preventing aggregation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 45 | pages = 17351–5 | date = November 2008 | pmid = 18987317 | pmc = 2579888 | doi = 10.1073/pnas.0809794105 | bibcode = 2008PNAS..10517351A | doi-access = free }}</ref> The active chaperonin role is in turn involved with specific chaperonin–substrate interactions that may be coupled to conformational rearrangements of the chaperonin.<ref name="KmiecikKolinski2011">{{cite journal | vauthors = Kmiecik S, Kolinski A | title = Simulation of chaperonin effect on protein folding: a shift from nucleation-condensation to framework mechanism | journal = Journal of the American Chemical Society | volume = 133 | issue = 26 | pages = 10283–9 | date = July 2011 | pmid = 21618995 | pmc = 3132998 | doi = 10.1021/ja203275f | bibcode = 2011JAChS.13310283K }}</ref><ref name="ChakrabortyChatila2010">{{cite journal | vauthors = Chakraborty K, Chatila M, Sinha J, Shi Q, Poschner BC, Sikor M, Jiang G, Lamb DC, Hartl FU, Hayer-Hartl M | display-authors = 6 | title = Chaperonin-catalyzed rescue of kinetically trapped states in protein folding | journal = Cell | volume = 142 | issue = 1 | pages = 112–22 | date = July 2010 | pmid = 20603018 | doi = 10.1016/j.cell.2010.05.027 | s2cid = 3859016 | doi-access = free }}</ref><ref name="ToddLorimer1996">{{cite journal | vauthors = Todd MJ, Lorimer GH, Thirumalai D | title = Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 9 | pages = 4030–5 | date = April 1996 | pmid = 8633011 | pmc = 39481 | doi = 10.1073/pnas.93.9.4030 | bibcode = 1996PNAS...93.4030T | doi-access = free }}</ref>

Probably the most popular model of the chaperonin active role is the iterative annealing mechanism (IAM), which focuses on the effect of iterative, and hydrophobic in nature, binding of the protein substrate to the chaperonin. According to computational simulation studies, the IAM leads to more productive folding by unfolding the substrate from misfolded conformations<ref name="ToddLorimer1996"/> or by prevention from protein misfolding through changing the folding pathway.<ref name="KmiecikKolinski2011" />

== Conservation of structural and functional homology ==
As mentioned, all cells contain chaperonins. 
* In bacteria, the archetype is the well-characterized chaperonin [[GroEL]] from ''[[E. coli]]''.
* In [[archaea]], the chaperonin is called the [[thermosome]].
* In [[eukarya]], the cytoplasmic chaperonin is called CCT (also called [[TRiC (complex)|TRiC]]).

These protein complexes appear to be essential for life in ''E. coli'', ''[[Saccharomyces cerevisiae]]'' and higher eukaryotes. While there are differences between eukaryotic, bacterial and archaeal chaperonins, the general structure and mechanism are conserved.<ref name=":0" />

=== Bacteriophage T4 morphogenesis ===

The gene product 31 (gp31) of [[Escherichia virus T4|bacteriophage T4]] is a protein required for bacteriophage morphogenesis that acts [[Catalysis|catalytically]] rather than being incorporated into the bacteriophage structure.<ref name="Snustad_1968">{{cite journal | vauthors = Snustad DP | title = Dominance interactions in Escherichia coli cells mixedly infected with bacteriophage T4D wild-type and amber mutants and their possible implications as to type of gene-product function: catalytic vs. stoichiometric | journal = Virology | volume = 35 | issue = 4 | pages = 550–63 | date = August 1968 | pmid = 4878023 | doi = 10.1016/0042-6822(68)90285-7 }}</ref> The bacterium ''E. coli'' is the host for bacteriophage T4.  The bacteriophage encoded gp31 protein appears to be homologous to the ''E. coli'' cochaperonin protein [[GroES]] and is able to substitute for it in the assembly of phage T4 virions during infection.<ref name = Marusich1998>{{cite journal | vauthors = Marusich EI, Kurochkina LP, Mesyanzhinov VV | title = Chaperones in bacteriophage T4 assembly. | journal = Biochemistry (Moscow) | date = April 1998 | volume = 63 | issue = 4 | pages = 399–406 | pmid = 9556522 | url = http://www.protein.bio.msu.ru/biokhimiya/contents/v63/full/63040473.html }}</ref>  Like GroES, gp31 forms a stable complex with [[GroEL]] chaperonin that is absolutely necessary for the folding and assembly ''in vivo'' of the bacteriophage T4 major capsid protein gp23.<ref name = Marusich1998/>

The main reason for the phage to need its own GroES homolog is that the gp23 protein is too large to fit into a conventional GroES cage. gp31 has longer loops that create a taller container.<ref>{{cite journal | vauthors = Bukau B, Horwich AL | title = The Hsp70 and Hsp60 chaperone machines | journal = Cell | volume = 92 | issue = 3 | pages = 351–66 | date = February 1998 | pmid = 9476895 | doi = 10.1016/S0092-8674(00)80928-9 | s2cid = 16526409 | doi-access = free }}</ref>

== Clinical significance ==
Human GroEL is the immunodominant antigen of patients with [[Legionellosis|Legionnaire's disease]],<ref name="PUB00001725">{{cite journal | vauthors = Hindersson P, Høiby N, Bangsborg J | title = Sequence analysis of the Legionella micdadei groELS operon | journal = FEMS Microbiology Letters | volume = 61 | issue = 1 | pages = 31–8 | date = January 1991 | pmid = 1672279 | doi = 10.1111/j.1574-6968.1991.tb04317.x | doi-access = free }}</ref> and is thought to play a role in the protection of the Legionella bacteria from oxygen [[radical (chemistry)|radical]]s within [[macrophage]]s. This hypothesis is based on the finding that the cpn60 gene is upregulated in response to [[hydrogen peroxide]], a source of oxygen radicals. Cpn60 has also been found to display strong antigenicity in many bacterial species<ref name="PUB00000632">{{cite journal | vauthors = Gor D, Mayfield JE | title = Cloning and nucleotide sequence of the Brucella abortus groE operon | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1130 | issue = 1 | pages = 120–2 | date = February 1992 | pmid = 1347461 | doi = 10.1016/0167-4781(92)90476-g }}</ref> and has the potential for inducing immune protection against unrelated bacterial infections.

== Examples ==

Human genes encoding proteins containing this domain include:
* [[BBS10]]
* [[CCT1]]; [[CCT2 (gene)|CCT2]]; [[CCT3]]; [[CCT4]]; [[CCT5 (gene)|CCT5]]; [[CCT6A]]; [[CCT6B]]; [[CCT7]]; [[CCT8]]
* [[CESK1]]
* [[HSPD1]]
* [[KCNMB3L]]
* [[CCT8L1]]; [[LOC401329]]
* [[MKKS]]
* [[FYVE finger-containing phosphoinositide kinase|PIP5K3]]

== See also ==
* [[Chaperone (protein)|Chaperone]]
* [[Heat shock protein]]
* [[Arthur L. Horwich]]

== Notes ==
{{notelist}}

== References ==
{{reflist}}

== External links ==
* [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb32_1.html more details...] {{Webarchive|url=https://web.archive.org/web/20110301024551/http://www.pdb.org/pdb/static.do?p=education_discussion%2Fmolecule_of_the_month%2Fpdb32_1.html |date=2011-03-01 }}
* {{MeshName|Chaperonins}}
* [http://www.cpndb.ca cpnDB: a chaperonin database]
* [http://people.cryst.bbk.ac.uk/~ubcg16z/cpn/elmovies.html Animations of activity of Chaperonins] {{Webarchive|url=https://web.archive.org/web/20210413043307/http://people.cryst.bbk.ac.uk/~ubcg16z/cpn/elmovies.html |date=2021-04-13 }}
*[https://web.archive.org/web/20160304043212/http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&index=17653&field=all&HM=&II=&PA=&form=&input= NIH Material on HSP60]
*[http://db.yeastgenome.org/cgi-bin/locus.pl?locus=HSP60 HSP60] {{Webarchive|url=https://web.archive.org/web/20080316025554/http://db.yeastgenome.org/cgi-bin/locus.pl?locus=HSP60 |date=2008-03-16 }}
*[http://flybase.bio.indiana.edu/reports/FBgn0015245.html HSP60 in Flies] {{Webarchive|url=https://web.archive.org/web/20080628202649/http://flybase.bio.indiana.edu/reports/FBgn0015245.html |date=2008-06-28 }}
*[http://biochem.uthscsa.edu/seale/Chap/chap.html The Chaperonin Home Page]
*[http://www.google.com/search?q=protein+data+bank&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a The Protein Data Bank]
*[http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=3.6.4.10 Enzyme Database on HSP60] {{Webarchive|url=https://web.archive.org/web/20210418233604/http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=3.6.4.10 |date=2021-04-18 }}
*[https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed HSP60 on Pub Med]
*[http://rgd.mcw.edu/tools/genes/genes_view.cgi?id=621314 HSP60 Gene Report]
* {{MeshName|HSP60+Heat-Shock+Proteins}}
{{InterPro content|IPR002423}}
{{Chaperones}}

[[Category:Heat shock proteins]]
[[Category:Moonlighting proteins]]
[[Category:Molecular chaperones]]
[[Category:Protein folding]]