Question

Describeon molecular level, what occurs during the two steps of protein folding. Be sure to include thermodynamic considerations.

Answer 1

After the complex process called translation proteins are synthesized in its primary structure. The amino acid sequences in the protein it self determines its structure. But the proteins need the help of another group of protein for proper folding. Chaperons are a group of proteins present in all organelles of eukaryotes. Hsp70 is a chaperon present in cytoplasm, BiP is a homolog present in Endoplasmic reticulum. Folding of proteins occur in ER.

increased unfolded proteins in the ER cause release of more chaperon from lumen. BiP is the chaperon present in the ER and it helps in the process of protein folding.

major steps in the process of protein folding by chaperon is ATP binding and ATP hydrolysis

1. ATP bound chaperon is in an open conformation,

The exposed hydrophobic substrate binding domain of the ATP bound chaperon bind with the hydrophobic region of the unfolded protein.

2. ATP hydrolysis occurs ATP converted to ADP

Chaperon in closed conformation, bind the substrate protein very tightly. The tight bounding facilitate protein folding.

Again the chaperon bind with ATP cause conformation change and the folded protein get released.

Thermodynamics of ATP hydrolysis.

ATP + H₂O ADP + Pi + Energy (-7.30 kcal/mol)