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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.
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.


== Classification ==
== Categories of chaperonins ==


===Group I===
===Group I===
Line 60: Line 60:


===Group III===
===Group III===
This family includes some archaeal Cpns that are related to Group II, but the opening is noncooperative in them.<ref name=":0" />


== Mechanism of action ==
== Mechanism of action ==

Revision as of 12:12, 6 December 2020

This article is about the protein family. For the human mitochondrial protein, see HSPD1.
TCP-1/cpn60 chaperonin family
Structure of the bacterial chaperonin GroEL.[1]
Identifiers
SymbolCpn60_TCP1
PfamPF00118
InterProIPR002423
PROSITEPDOC00610
SCOP21grl / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1sx3K:23-525 1kpoZ:23-525 1fyaA:190-375

1gruH:23-525 1xckF:23-525 1kp8E:23-525 1pcqJ:23-524 1aonJ:23-524 1mnfI:23-525 1svtJ:23-524 2c7dK:23-525 1dkdC:190-335 1j4zL:23-525 1oelE:23-524 2c7cH:23-525 1gr5H:23-525 1sx4E:23-524 1kid :190-375 1gr6F:23-525 1ss8B:23-524 1fy9A:190-375 1dk7A:190-335 1jon :190-335 1la1A:187-378 1iokA:23-526 1wf4e:22-526 1we3E:22-526 1sjpB:42-522 1srvA:1-143 1a6dB:33-521 1a6eB:33-521 1e0rB:215-366 1ass :214-364

1asx :214-364 1gn1H:210-380 1gmlB:210-380

HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass.[2] 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, called molecular chaperones.[3][4]

Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional tertiary structure. The energy to fold proteins is supplied by adenosine triphosphate (ATP). Chaperonin proteins may also tag misfolded proteins to be degraded.[4]

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.

Classification

Group I

GroES/GroEL complex (side)

Group I chaperonins 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-AlF3. It's 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.[5]

Group II

Thermosome chaperonin II, hetero16mer, Sulfolobus solfataricus.

Group II chaperonins, found in the eukaryotic cytosol and in archaea, are more poorly characterized.

  • The complex in archaea is called the thermosome. A homo-oligomer, it is regarded as the prototypical type II chaperonin.
  • TRiC, the eukaryotic chaperonin, is composed of two rings of eight different though related 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.

Mm cpn (Methanococcus maripaludis chaperonin), found in the archaea Methanococcus maripaludis, 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.[6]

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.

Group III

This family includes some archaeal Cpns that are related to Group II, but the opening is noncooperative in them.[4]

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.[7] 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.[8] The active chaperonin role is in turn involved with specific chaperonin–substrate interactions that may be coupled to conformational rearrangements of the chaperonin.[9][10][11]

Probably the most popular model of the chaperonin active role is the iterative annealing mechanism (IAM), which focus 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[11] or by prevention from protein misfolding through changing the folding pathway.[9]

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).

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.[4]

Bacteriophage T4 morphogenesis

Snustad[12] identified gene product 31 (gp31) of bacteriophage T4 as a protein required for bacteriophage morphogenesis that acts catalytically rather than being incorporated into the bacteriophage structure. 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 able to substitute for it in the assembly of phage T4 virions during infection.[13] 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.[13]

See also

References

  1. ^ Braig K, Otwinowski Z, Hegde R, et al. (October 1994). "The crystal structure of the bacterial chaperonin GroEL at 2.8 A". Nature. 371 (6498): 578–86. doi:10.1038/371578a0. PMID 7935790.
  2. ^ Cite error: The named reference seven was invoked but never defined (see the help page).
  3. ^ Howard Hughes Investigators: Arthur L. Horwich, M.D.
  4. ^ a b c d Robb, Frank T.; Alberto J. L. Macario; Yohda, Masafumi; Macario, Everly Conway de (2019-03-15). "Bridging human chaperonopathies and microbial chaperonins". Communications Biology. 2 (1): 103. doi:10.1038/s42003-019-0318-5. ISSN 2399-3642. PMC 6420498. PMID 30911678.
  5. ^ Fenton WA, Horwich AL (May 2003). "Chaperonin-mediated protein folding: fate of substrate polypeptide". Q. Rev. Biophys. 36 (2): 229–56. doi:10.1017/S0033583503003883. PMID 14686103.
  6. ^ Kusmierczyk AR, Martin J (May 2003). "Nucleotide-dependent protein folding in the type II chaperonin from the mesophilic archaeon Methanococcus maripaludis". Biochem. J. 371 (3): 669–673. doi:10.1042/BJ20030230. PMC 1223359. PMID 12628000.
  7. ^ Hartl, FU; Hayer-Hartl, M (2009). "Converging concepts of protein folding in vitro and in vivo". Nature Structural & Molecular Biology. 16 (6): 574–581. doi:10.1038/nsmb.1591. PMID 19491934.
  8. ^ Apetri, AC; Horwich, AL (2008). "Chaperonin chamber accelerates protein folding through passive action of preventing aggregation". Proceedings of the National Academy of Sciences. 105 (45): 17351–17355. doi:10.1073/pnas.0809794105. PMC 2579888. PMID 18987317.
  9. ^ a b Kmiecik, S; Kolinski, A (2011). "Simulation of Chaperonin Effect on Protein Folding: A Shift from Nucleation–Condensation to Framework Mechanism". Journal of the American Chemical Society. 133 (26): 10283–10289. doi:10.1021/ja203275f. PMC 3132998. PMID 21618995.
  10. ^ Chakraborty, K; Chatila, M; Sinha, J; Shi, Q; Poschner, BC; Sikor, M; Jiang, G; Lamb, DC; Hartl, FU; Hayer-Hartl, M (2010). "Chaperonin-Catalyzed Rescue of Kinetically Trapped States in Protein Folding". Cell. 142 (1): 112–122. doi:10.1016/j.cell.2010.05.027. PMID 20603018.
  11. ^ a b Todd, MJ; Lorimer, GH; Thirumalai, D. (1996). "Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism". Proceedings of the National Academy of Sciences. 93 (9): 4030–4035. doi:10.1073/pnas.93.9.4030. ISSN 0027-8424. PMC 39481. PMID 8633011.
  12. ^ Snustad DP. 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. 1968;35(4):550-563. doi:10.1016/0042-6822(68)90285-7
  13. ^ a b Marusich EI, Kurochkina LP, Mesyanzhinov VV. Chaperones in bacteriophage T4 assembly. Biochemistry (Mosc). 1998;63(4):399-406
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