Molecular Chaperones and Protein Folding

As they are synthesized in the cell, most proteins do not fold spontaneously into their native conformation but require a special class of proteins called chaperones to help fold them.

Of the several types of molecular chaperones found in prokaryotes and eukaryotes, the two major families are the heat shock proteins - hsp70 and hsp60.

In a correctly folded protein, hydrophobic patches are buried in the interior.

In misfolded proteins, hydrophobic patches are exposed. Such patches on different protein molecules can bind to each other, leading to irreversible protein aggregation.

Chaperones recognize these exposed hydrophobic patches and prevent protein aggregation, facilitating the folding of the proteins.

The hsp70 machinery often acts before the protein leaves the ribosome, with each ATP-bound monomer recognizing a small stretch of hydrophobic amino acids on a protein’s surface. 

A set of smaller hsp40 proteins interacts with this complex and triggers ATP hydrolysis. As a result, parts of hsp70 come together like jaws, trapping the unfolded protein inside. 

Next, ATP binds the complex again inducing the dissociation of hsp70 and releasing the bound polypeptide, allowing it a chanc