Chaperonin
Encyclopedia
Chaperonins are proteins that fold and unfold other proteins. Newly made proteins usually must fold
from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones. The energy to fold proteins is supplied by adenosine triphosphate
(ATP).
Each ring is composed of either 7, 8 or 9 subunits depending on the organism in which the chaperonin is found.
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/GroES may not be able to undo protein aggregates, but kinetically it competes in the pathway of misfolding and aggregation, thereby preventing aggregate formation.
and in archaea
, are more poorly characterized.
TRiC (TCP-1 Ring Complex, also called CCT for chaperonin containing TCP-1), the eukaryotic chaperonin, is composed 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.
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.
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.
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.
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones. The energy to fold proteins is supplied by adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP).
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.
Group I
Group I chaperonins are found in bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
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.
- GroELGroELGroEL belongs to the chaperonin family of molecular chaperones, and is found in a large number of bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES...
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. - GroESGroESHeat shock 10 kDa protein 1 also known as chaperonin 10 or early-pregnancy factor is a protein that in humans is encoded by the HSPE1 gene. The homolog in E...
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.
Group II
Group II chaperonins, found in the eukaryotic cytosolCytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
and in archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
, are more poorly characterized.
TRiC (TCP-1 Ring Complex, also called CCT for chaperonin containing TCP-1), the eukaryotic chaperonin, is composed 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.
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.
Mechanism of action
Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatic hydrolysisHydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
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.
Conservation of structural and functional homology
As mentioned, all cells contain chaperonins.- In bacteria, the archetype is the well-characterized chaperonin GroELGroELGroEL belongs to the chaperonin family of molecular chaperones, and is found in a large number of bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES...
from E. coli. - In archaeaArchaeaThe Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
, the chaperonin is called the thermosome. - In eukarya, the chaperonin is called CCT (also called TRiCTRICTRIC may refer to:* Three Rivers Inline Club, a not-for-profit inline skating club in Pittsburgh, Pennsylvania* Television and Radio Industries Club, a UK industry association* TRIC, a fictional nightclub from the television series One Tree Hill...
or c-cpn).
These protein complexes appear to be essential for life in E. coli, Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
and higher eukaryotes. While there are differences between eukaryotic, bacterial and archaeal chaperonins, the general structure and mechanism are conserved.