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Chaperonin

From Wikipedia, the free encyclopedia
This article is about the protein family. For the human mitochondrial protein, seeHSPD1.
TCP-1/cpn60 chaperonin family
Structure of the bacterial chaperonin GroEL.[1]
Identifiers
SymbolCpn60_TCP1
PfamPF00118
InterProIPR002423
PROSITEPDOC00610
CATH5GW5
SCOP21grl/SCOPe/SUPFAM
CDDcd00309
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
PDB1sx3K:23-5251kpoZ:23-5251fyaA:190-375

1gruH:23-5251xckF:23-5251kp8E:23-525 1pcqJ:23-5241aonJ:23-5241mnfI:23-525 1svtJ:23-5242c7dK:23-5251dkdC:190-335 1j4zL:23-5251oelE:23-5242c7cH:23-525 1gr5H:23-5251sx4E:23-5241kid:190-375 1gr6F:23-5251ss8B:23-5241fy9A:190-375 1dk7A:190-3351jon:190-3351la1A:187-378 1iokA:23-5261wf4e:22-5261we3E:22-526 1sjpB:42-5221srvA:1-1431a6dB:33-521 1a6eB:33-5211e0rB:215-3661ass:214-364

1asx:214-3641gn1H:210-3801gmlB:210-380

HSP60,also known aschaperonins(Cpn), is a family ofheat shock proteinsoriginally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 belong to a large class of molecules that assist protein folding, calledmolecular chaperones.[2][3]

Newly made proteins usually mustfoldfrom a linear chain of amino acids into a three-dimensionaltertiary 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 ofadenosine triphosphate(ATP). Chaperonin proteins may also tag misfolded proteins to be degraded.[3]

Structure

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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.[4]

The original chaperonin is proposed to have evolved from aperoxiredoxin.[5]

Classification

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Group I

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GroES/GroEL complex (side)

Group I chaperonins (Cpn60)[a]are found inbacteriaas well asorganellesofendosymbioticorigin:chloroplastsandmitochondria.

The GroEL/GroES complex inE. coliis a Group I chaperonin and the best characterized large (~ 1 MDa) chaperonin complex.

  • GroELis a double-ring 14mer with a greasyhydrophobicpatch 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 ortransition stateanalogues of ATP hydrolysis, such as ADP-AlF3.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.[6]

The Cpn60 subfamily was discovered in 1988.[7]It was sequenced in 1992. The cpn10 and cpn60 oligomers also require Mg2+-ATP in order to interact to form a functional complex.[8]The binding of cpn10 to cpn60 inhibits the weakATPaseactivity of cpn60.[9]

TheRuBisCOsubunit binding protein is a member of this family.[10]The crystal structure ofEscherichia coliGroEL has been resolved to 2.8 Å.[11]

Some bacteria use multiple copies of this chaperonin, probably for different peptides.[4]

Group II

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Structure ofSaccharomyces cerevisiaeTRiC in the AMP-PNP bound state (PDB:5GW5​).[12]

Group II chaperonins (TCP-1), found in theeukaryoticcytosoland inarchaea,are more poorly characterized.

  • The complex in archaea is called thethermosome.A homo-16mer in some archaea, it is regarded as the prototypical type II chaperonin.[b]
  • TRiC,the eukaryotic chaperonin, is composed of two rings of eight different thoughrelated subunits,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 maripaludischaperonin (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.[13]

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.[3]

Other families

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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.[3][4]

A Group I chaperonin gp146 fromphage ELdoes not use a lid, and its donut interface is more similar to Group II. It might represent another ancient type of chaperonin.[14]

Mechanism of action

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Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatichydrolysisof 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.[15]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.[16]The active chaperonin role is in turn involved with specific chaperonin–substrate interactions that may be coupled to conformational rearrangements of the chaperonin.[17][18][19]

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[19]or by prevention from protein misfolding through changing the folding pathway.[17]

Conservation of structural and functional homology

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As mentioned, all cells contain chaperonins.

  • In bacteria, the archetype is the well-characterized chaperoninGroELfromE. coli.
  • Inarchaea,the chaperonin is called thethermosome.
  • Ineukarya,the cytoplasmic chaperonin is called CCT (also calledTRiC).

These protein complexes appear to be essential for life inE. coli,Saccharomyces cerevisiaeand higher eukaryotes. While there are differences between eukaryotic, bacterial and archaeal chaperonins, the general structure and mechanism are conserved.[3]

Bacteriophage T4 morphogenesis

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The gene product 31 (gp31) ofbacteriophage T4is a protein required for bacteriophage morphogenesis that actscatalyticallyrather than being incorporated into the bacteriophage structure.[20]The bacteriumE. coliis the host for bacteriophage T4. The bacteriophage encoded gp31 protein appears to be homologous to theE. colicochaperonin proteinGroESand is able to substitute for it in the assembly of phage T4 virions during infection.[21]Like GroES, gp31 forms a stable complex withGroELchaperonin that is absolutely necessary for the folding and assemblyin vivoof the bacteriophage T4 major capsid protein gp23.[21]

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.[22]

Clinical significance

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Human GroEL is the immunodominant antigen of patients withLegionnaire's disease,[10]and is thought to play a role in the protection of the Legionella bacteria from oxygenradicalswithinmacrophages.This hypothesis is based on the finding that the cpn60 gene is upregulated in response tohydrogen peroxide,a source of oxygen radicals. Cpn60 has also been found to display strong antigenicity in many bacterial species[23]and has the potential for inducing immune protection against unrelated bacterial infections.

Examples

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Human genes encoding proteins containing this domain include:

See also

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Notes

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  1. ^The GroEL family is referred to, by InterPro, as Cpn60. However, CDD uses Cpn60 to refer to the Group II proteins in archaea.
  2. ^Some archaeons have evolved to use, like eukaryotes, different subunits.Methanosarcina acetivoransis known to have five types of subunits.[3]The ancestor to eukarotic TriC is thought to have two.[5]

References

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  1. ^Braig K, Otwinowski Z, Hegde R, Boisvert DC, Joachimiak A, Horwich AL, Sigler PB (October 1994). "The crystal structure of the bacterial chaperonin GroEL at 2.8 A".Nature.371(6498): 578–86.Bibcode:1994Natur.371..578B.doi:10.1038/371578a0.PMID7935790.S2CID4341993.
  2. ^"Howard Hughes Investigators: Arthur L. Horwich, M.D."Archived fromthe originalon 2019-07-26.Retrieved2011-09-12.
  3. ^abcdefConway de Macario E, Yohda M, Macario AJ, Robb FT (2019-03-15)."Bridging human chaperonopathies and microbial chaperonins".Communications Biology.2(1): 103.doi:10.1038/s42003-019-0318-5.PMC6420498.PMID30911678.
  4. ^abcAnsari MY, Mande SC (2018)."A Glimpse Into the Structure and Function of Atypical Type I Chaperonins".Frontiers in Molecular Biosciences.5:31.doi:10.3389/fmolb.2018.00031.PMC5904260.PMID29696145.
  5. ^abWillison, KR (5 October 2018). "The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its mechanism that folds actin into a protein spring".The Biochemical Journal.475(19): 3009–3034.doi:10.1042/BCJ20170378.hdl:10044/1/63924.PMID30291170.S2CID52923821.
  6. ^Fenton WA, Horwich AL (May 2003). "Chaperonin-mediated protein folding: fate of substrate polypeptide".Quarterly Reviews of Biophysics.36(2): 229–56.doi:10.1017/S0033583503003883.PMID14686103.S2CID10328521.
  7. ^Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, et al. (May 1988). "Homologous plant and bacterial proteins chaperone oligomeric protein assembly".Nature.333(6171): 330–4.Bibcode:1988Natur.333..330H.doi:10.1038/333330a0.PMID2897629.S2CID4325057.
  8. ^Prasad TK, Stewart CR (March 1992). "cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin HSP60 and gene expression during seed germination and heat shock".Plant Molecular Biology.18(5): 873–85.doi:10.1007/BF00019202.PMID1349837.S2CID40768099.
  9. ^Schmidt A, Schiesswohl M, Völker U, Hecker M, Schumann W (June 1992)."Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis".Journal of Bacteriology.174(12): 3993–9.doi:10.1128/jb.174.12.3993-3999.1992.PMC206108.PMID1350777.
  10. ^abHindersson P, Høiby N, Bangsborg J (January 1991)."Sequence analysis of the Legionella micdadei groELS operon".FEMS Microbiology Letters.61(1): 31–8.doi:10.1111/j.1574-6968.1991.tb04317.x.PMID1672279.
  11. ^Braig K, Otwinowski Z, Hegde R, Boisvert DC, Joachimiak A, Horwich AL, Sigler PB (October 1994). "The crystal structure of the bacterial chaperonin GroEL at 2.8 A".Nature.371(6498): 578–86.Bibcode:1994Natur.371..578B.doi:10.1038/371578a0.PMID7935790.S2CID4341993.
  12. ^Zang Y, Jin M, Wang H, Cui Z, Kong L, Liu C, Cong Y (December 2016). "Staggered ATP binding mechanism of eukaryotic chaperonin TRiC (CCT) revealed through high-resolution cryo-EM".Nature Structural & Molecular Biology.23(12). Springer Science and Business Media LLC: 1083–1091.doi:10.1038/nsmb.3309.PMID27775711.S2CID12001964.
  13. ^Kusmierczyk AR, Martin J (May 2003)."Nucleotide-dependent protein folding in the type II chaperonin from the mesophilic archaeon Methanococcus maripaludis".The Biochemical Journal.371(Pt 3): 669–73.doi:10.1042/BJ20030230.PMC1223359.PMID12628000.
  14. ^Bracher A, Paul SS, Wang H, Wischnewski N, Hartl FU, Hayer-Hartl M (27 April 2020)."Structure and conformational cycle of a bacteriophage-encoded chaperonin".PLOS ONE.15(4): e0230090.Bibcode:2020PLoSO..1530090B.doi:10.1371/journal.pone.0230090.PMC7185714.PMID32339190.
  15. ^Hartl FU, Hayer-Hartl M (June 2009). "Converging concepts of protein folding in vitro and in vivo".Nature Structural & Molecular Biology.16(6): 574–81.doi:10.1038/nsmb.1591.PMID19491934.S2CID205522841.
  16. ^Apetri AC, Horwich AL (November 2008)."Chaperonin chamber accelerates protein folding through passive action of preventing aggregation".Proceedings of the National Academy of Sciences of the United States of America.105(45): 17351–5.Bibcode:2008PNAS..10517351A.doi:10.1073/pnas.0809794105.PMC2579888.PMID18987317.
  17. ^abKmiecik S, Kolinski A (July 2011)."Simulation of chaperonin effect on protein folding: a shift from nucleation-condensation to framework mechanism".Journal of the American Chemical Society.133(26): 10283–9.doi:10.1021/ja203275f.PMC3132998.PMID21618995.
  18. ^Chakraborty K, Chatila M, Sinha J, Shi Q, Poschner BC, Sikor M, et al. (July 2010)."Chaperonin-catalyzed rescue of kinetically trapped states in protein folding".Cell.142(1): 112–22.doi:10.1016/j.cell.2010.05.027.PMID20603018.S2CID3859016.
  19. ^abTodd MJ, Lorimer GH, Thirumalai D (April 1996)."Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism".Proceedings of the National Academy of Sciences of the United States of America.93(9): 4030–5.Bibcode:1996PNAS...93.4030T.doi:10.1073/pnas.93.9.4030.PMC39481.PMID8633011.
  20. ^Snustad DP (August 1968). "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".Virology.35(4): 550–63.doi:10.1016/0042-6822(68)90285-7.PMID4878023.
  21. ^abMarusich EI, Kurochkina LP, Mesyanzhinov VV (April 1998)."Chaperones in bacteriophage T4 assembly".Biochemistry (Moscow).63(4): 399–406.PMID9556522.
  22. ^Bukau B, Horwich AL (February 1998)."The Hsp70 and Hsp60 chaperone machines".Cell.92(3): 351–66.doi:10.1016/S0092-8674(00)80928-9.PMID9476895.S2CID16526409.
  23. ^Gor D, Mayfield JE (February 1992). "Cloning and nucleotide sequence of the Brucella abortus groE operon".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1130(1): 120–2.doi:10.1016/0167-4781(92)90476-g.PMID1347461.
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