Biological complexity: making insulin fold properly (Introduction)

by David Turell , Saturday, January 26, 2019, 00:51 (2129 days ago) @ David Turell

It is not automatic an d requires shepherding by a specific protein in Beta cells:

https://www.sciencedaily.com/releases/2019/01/190125094248.htm

"Insulin is produced in the beta cells of the pancreas. The hormone is produced as a precursor called proinsulin. For proinsulin to mature into functional insulin, it needs to be folded and processed correctly to acquire the right structure with assistance from proteins that are termed chaperones. The researchers have now discovered and identified such a chaperone. A proinsulin chaperone termed glucose-regulated protein GRP94.

''Even though proinsulin has a relatively short sequence, it still needs help acquiring the right structure to become mature, functional insulin. However, several other studies have shown that proinsulin can be folded without help from proteins in artificial cell-free conditions. Yet, our study conducted in live cells shows that proinsulin is not folded correctly and does not acquire the right structure without help from GRP94,' says last author of the study, Associate Professor Michal Tomasz Marzec from the Department of Biomedical Sciences at the University of Copenhagen.

"In the study the researchers removed or inhibited the protein GRP94 in to see what happened with the proinsulin and the cells. They observed that the proinsulin was not folded correctly and the beta cells did not secrete sufficient amounts of insulin. The researchers were surprised though to learn that removal of GRP94 did not affect cell viability. Nothing happened to the cells after they had removed the protein.

''This is surprising, because one would anticipate that the beta cells would die from stress when huge amounts of misfolded proinsulin accumulate inside the cells. It is like removing the bearing beam without weakening the construction. This indicates that the GRP94 protein plays a very specialized function and that beta cells are well-prepared to mount effective responses to deal with consequences of misfolding of proinsulin. "

Comment: This process must be done in one specific way by one specific protein, and others are probably present and not yet found. Some protein molecules make folds automatically, but in this case guidance is required. Only design can create such a system.