Question

Explain how chaperones work to finalize the shape and structure of a protein prior to its full function.

Good examples to use are GroEL and GroES

Answer 1

• Molecular cheprones are proteins which associate to unfolded or incompletely folded proteins which ensures correct folding as well as prevents their aggregation.
• Cheprones also assist refolding of oligomeric structures, stress denatured proteins and protein trafficking.
• Cheprones are present ubiquitously in prokaryotes and eukaryotes, and are usually included in heat shock proteins as they are synthesise after a brief exposure to an elevated temperature.
• Two major families of molecular cheprones include Hsp60 and Hsp 70 family.
• Hsp 70 family : members of Hsp 70 family bind to 7 hydrophobic amino acids of protein before it leaves the ribosome. These contain two domains, one having ATPase activity and other which binds to hydrophobic stretch of unfolded polypeptide. These are essential for protein translocation.
• Hsp 60 family : Also known as chaperonins, form barrel shaped structure which acts after complete synthesis of protein and bind to protein either in unfolded, incompletely or incorrectly folded forms only. These chepronins provide favourable environment for correct refolding of proteins. Ring structure containing multiple subunits forms a cylindrical structure (eg. GroEL in E.coli) which associates to a heptamer forming ring like structure(GroES) known as co chaperonin.
• Misfolded protein binds to GroEL at one end followed by binding of ATP and GroES.
• ATP hydrolysis occurs as a result of protein folding-unfolding in central cavity.
• Subsequent ATP binding and hydrolysis releases GroES as well correctly folded protein.