Molecular chaperones are needed to favour correct folding, not aggregation.

1. Hydrophobic patches on nascent/unfolded proteins are recognised by Heat shock protein 40 family members, which… 2. …deliver the substrate to ATP-bound (OPEN conformation) Heat shock cognate protein 70 (Hsc70 chaperone) and stimulate the ATPase activity of Hsc70… 3. …resulting in ADP-bound (CLOSED conformation) Hsc70 shielding the hydrophobic patches of the substrate, preventing aggregation, and allowing time for the hydrophilic parts of the substrate to fold. 4. Upon nucleotide exchange, Hsc70 adopts its open conformation, releasing the substrate, with folded soluble structures: this partly folded protein may now snap into its final conformation.