Question

Imagine conducting the following experiment. Take a sample of the native folded peptide and measure the amount of peptide required to inhibit the activity of a potassium channel, say the Kv4.2 channel, by 50%. We will call this value the IC50 value. For our peptide, IC50 = 5 nM for the Kv4.2 channel. Treat the peptide with a mixture of 2-mercaptoethanol and guanidine hydrochloride. Remove the 2-mercatoethanol and then the guanidine hydrochloride to allow the peptide to refold. Treat the Kv4.2 channel with the refolded peptide and measure the IC50 value. If the IC50 value is now 250 nM, does this peptide sequence obey the Anfinsen dogma? Explain.

Answer 1

Anfinsen's dogma suggests that "in the native physiological environment small globular proteins are able to attain their native structure simply on the basis of the amino acid sequence". Thus, following Anfinsen's dogma, an unfolded small globular protein would regain its native state without any external help if it is maintained in its actual physiological environment.

Assuming that the above experiment was carried out in the natural physiological environment of the peptide sample, it was observed that the IC50 value was significantly increased after the treatment. This indicates that refolding of the protein did not occur very effectively. Only 2% of the protein molecules were able to refold to the native shape required for inhibiting the activity of the potassium channel. Thus, the peptide sequence did not obey Anfinsen's dogma.