Protein folding
Under the appropriate physiological conditions, proteins fold spontaneously into their native conformation. As there is no requirement of the exterior templates, this implies that the primary structure of the protein dictates the 3-dimensional structure of it. From experiments with the protein RNase A it has been observed that it is basically the internal residues of protein which direct it’s folding to the native conformation. The alteration of surface residues by the mutation is less probable to affect folding than changes to internal residues. It has been observed that the protein folding can be driven primarily by hydrophobic forces. Proteins fold into their inhabitant conformation through an ordered set of pathways instead of random exploration of all the possible conformations until correct one is stumbled upon.
However proteins can fold in vitro (in laboratory) without the presence of accessory proteins, this process can take hours to days. In vivo this process requires only few minutes as the cells contain accessory proteins that assist the polypeptides to fold to their inhabitant conformation. There are 3 main classes of protein folding accessory proteins:
- Protein disul?de isomerases catalyze disul?de the interchange reactions, thus facilitating the shuf?ing of disul?de bonds in protein until they achieve their proper pairing.
- Peptidyl prolyl cis–trans isomerases catalyze otherwise slow inter conversion of Xaa–Pro peptide bonds in between their cis and trans conformations, thus accelerating the folding of Pro-containing polypeptides. The one of the classes of peptidyl prolyl cis trans isomerases is inhibited by immune suppressive drug cyclosporin A.
- Molecular chaperones, this include proteins like the heat shock proteins 70 (Hsp 70), the chaperonins,and lectins calnexin and calreticulin. These prevent improper folding and aggregation of proteins which may occur as internal hydrophobic regions are exposed to one another.