Question: Hi Sam! Having read your answer to libby12's question on things happening after the formation of primary polypeptides, could I make a detailed inquiry as to whether one primary structure can only lead to one specific shape of tertiary structure? Or alternatively, if the primary structure have the potential to fold into different proteins, but only directed by its environment or interaction with other molecules, such as Chaperone, which is mentioned by Toby. @Toby Thank you!

Sam Lear answered on 23 Jun 2014:

Hi amandazzh,

Protein folding is a very complex process and there is still a lot of research in this area as it is not completely understood.

As far as I understand proteins in nature have evolved exclusively to exist in a single stable folded shape. It is this shape that dictates how the protein behaves. In some cases however, proteins can end up in more stable shapes than evolution has selected for them. These are generally called ‘misfolded’ proteins, and can often cause problems.

Misfolded proteins are thought to be responsible for a number of diseases including Alzheimer’s disease and Creutzfeldt–Jakob disease (CJD).

The effect of the environment of a protein on it’s folding is also an interesting consideration. While it is certainly true that chaperones are important for the correct folding of some proteins, as Tobias said lots of proteins seem to contain all the ‘information’ they need to be able to fold by themselves in solution.

The misfolded protein thought to be responsible for CJD is called a ‘prion’. Prions are fascinating because their presence somehow causes the misfolding of other proteins into the more stable (toxic) prion state.

So in answer to your question: as far as I am aware, naturally occurring proteins cannot exist in more than one stable form, but they can sometimes misfold into a shape that is more stable than the one they originally evolved to exist in.

Perhaps when we know more about protein folding it will be possible to design artificial proteins that can fold into a number of different states with equal stability?