Protein Folding

In a newly synthesized peptide, interactions between its constituent amino acids guide its folding into a stable three-dimensional structure called the native conformation, often its functional form.

First, the linear polypeptide chain folds into alpha-helices and beta-sheets through hydrogen bonding between amino acid residues.

Hydrophobic side chains jutting out of the helices or beta-sheets come together, removing surrounding water molecules. As a result, the polypeptide is packed into a loosely folded intermediate with a hydrophobic core.

Polar residues on the surface make additional hydrogen bonds and ionic interactions, while adjacent cysteines form covalent disulfide bonds to stabilize the protein in its native conformation.

For proteins with multiple cysteines, protein disulfide isomerase enzyme catalyzes the rapid exchange of thiol groups, enabling correct disulfide bond formation.

Most proteins do not fold by themselves and are helped by heat shock proteins and chaperonins.

These molecular chaperones speed up the folding process by binding the unfolded peptide and preventing aggregation or providing a microenvironment where the peptide can fold into its native conformation.