Protein folding accessory proteins: Molecular chaperones, prolyl cis trans isomerase and protein disulphide isomerase

Three main classes of protein folding accessory proteins

i) Molecular chaperones include heat shock proteins 70 (Hsp 70), the chaperonins and nucleoplasmins.

Function: prevent the improper folding and aggregation of proteins.

Chaperones

Chaperonins: are cylindrical protein complexes that contain chambers in which newly synthesised protein can fold without interaction from other macromolecules.

Eg: TRiC chaperonin: assist in 15% of polypeptide folding in mammalian cell.

Families of Molecular Chaperones

1. Small heat shock proteins (hsp25)

• protect against cellular stress
• prevent aggregation in the lens (cataract)

2. Hsp60 system (cpn60, GroEL) ATPase

• protein folding

3. Hsp70 system (DnaK, BiP) ATPase

• stabilization of extended chains
• membrane translocation
• regulation of the heat shock response

4. Hsp90 ATPase

• binding and stabilization/ regulation of steroid receptors, protein kinases

5. Hsp100 (Clp) ATPase

• thermotolerance, proteolysis, resolubilization of aggregates

6. Calnexin, calreticulin

• glycoprotein maturation in the ER
• quality control

ii) Protein prolyl cis-trans isomerase

In proline containing polypeptides, the conversion of X-proline peptide bonds between their cis and trans confirmation is catalyzed by this protein.

 Protein prolyl cis-trans isomerase

iii) Protein disulphide isomerase

Catalyse shuffling of disulphide bonds in a protein until it attains correct pairing or folding.

Protein disulphide isomerase (PDI)