Prefoldin (GimC) is a superfamily of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s used in

protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

complexes. It is classified as a heterohexameric molecular chaperone in both

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

and

eukarya Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

, including

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s. A prefoldin molecule works as a transfer protein in conjunction with a molecule of

chaperonin HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 bel ...

to form a chaperone complex and correctly fold other nascent proteins. One of prefoldin's main uses in eukarya is the formation of molecules of

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

for use in the eukaryotic

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

Purpose and uses

Prefoldin is one family of chaperone proteins found in the domains of eukarya and archaea. Prefoldin acts in combination with other molecules to promote protein folding in cells where there are many other competing pathways for folding. Chaperone proteins perform non-covalent assembly of other polypeptide-containing structures ''in vivo''. They are implicated in the folding of most other proteins. In archaea, prefoldins are believed to function in combination with group II chaperonins in ''de novo''

. In eukarya however, prefoldins have acquired a more specific function: they are used to establish correct tubular assembly for many tubular proteins, such as

. Actin accounts for 5-10% of all protein found in eukaryotic cells, which therefore means that prefoldin is quite prevalent in the cells. Actin is made of two strings of beads wound round each other and is one of the three main parts of the

of eukaryotic cells. Prefoldin bonds specifically to cytosolic chaperonin protein. This complex of prefoldin and chaperonin then forms molecules of actin in the cytosol. The prefoldin acts as a transporter molecule that transports bound, unfolded target proteins to the chaperonin (C-CPN) molecule. For example, the prefoldin that is used in the formation of actin also transfers α or β tubulin to a cytosolic chaperonin. The prefoldin, however, does not form a ternary complex with tubulin and chaperonin. Once the tubulins are in contact with the chaperonin, the prefoldin automatically lets go and leaves the active site, due to its high affinity for the chaperonin molecule. Once the prefoldin is in contact with the chaperonin protein, it loses its affinity for the unfolded target protein. Prefoldin is triggered only to bind to nonnative target proteins in the cytosol so that it will only bind to unfolded proteins. Unlike many other molecular chaperones, prefoldin does not use chemical energy, in the form of

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...

(ATP), to promote protein folding.

Discovery

Prefoldin was found by the laboratory of Nicholas J. Cowan from the Department of Biochemistry at the

New York University New York University (NYU) is a private research university in New York City. Chartered in 1831 by the New York State Legislature, NYU was founded by a group of New Yorkers led by then-Secretary of the Treasury Albert Gallatin. In 1832, the ...

Medical Center. It was discovered using

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

. Unfolded labeled β-actin from bovine testes was put into solution. This solution contained an excess of cytosolic chaperonin (C-CPN), a eukaryotic chaperone protein necessary for actin folding. After gel filtration of the actin, the actin complex, consisting of actin and its bonded proteins, began to form and the molecular weight of the complex was observed. Gel electrophoresis was used to analyze the protein complex, the complex formed a single band that was excised and ran on an SDS gel. It resolved into five bands, therefore proving that a heterooligomeric protein is used to bind to unfolded actin. An archaeal homolog of prefoldin that also functions as a molecular chaperone has been identified. Eukaryotic prefoldin likely evolved from archaea, as it is not present (or has been lost) from bacteria.

Structure

Prefoldin is a hetero hexameric protein consisting of two α subunits and four β subunits. The beta subunits contain 120

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

residues each, while the α subunits contain 140 amino acid residues each. Each subunit was found to have a width of 8.4 nm in the archaea ''Methanococcus thermoautrophicum''. The height was calculated at 1.8-2.6 nm. The subunits are arranged by hydrophobic interactions with two β barrels at the center and coiled-coil α helices protruding down from them as if it were a

jellyfish Jellyfish and sea jellies are the informal common names given to the medusa-phase of certain gelatinous members of the subphylum Medusozoa, a major part of the phylum Cnidaria. Jellyfish are mainly free-swimming marine animals with umbrella- ...

. The lower "tentacles" of the jellyfish shape is the interface between prefoldin and chaperonin.

Purpose and uses

Discovery

Structure

References

See also