New Insights Into Hidden World Of Protein Folding

But researchers have been puzzled by how the long, linear proteins cranked out by the ribosome Language Software
factories in a cell are folded into the shapes they must assume to perform their function. They only have known that for many of the most complex and essential proteins, the folding takes place out of sight, hidden in the inner cavity of a type of molecule called a chaperonin.Now Stanford researchers have begun prying open the lid, literally, on the inner workings of chaperonin molecules by deducing the mechanism by which the lid operates on a barrel-shaped chaperonin called TRiC.Understanding how the lid opens and closes really helps us understand how everything moves inside the chaperonin, said Judith Frydman, associate professor of biology and one of two senior authors of a paper published online recently in Nature Structural Molecular Biology.This is just the beginning, but now we can start to understand how the protein is pushed inside the cavity of the chaperonin and what this folding chamber looks like, Frydman said. Learning how a protein is manipulated inside TRiC while it is being folded is a crucial step in Frydman's larger plan.Our goal is to eventually exert control, she said. If we could re-engineer the chaperonin to either fold better misfolded proteins or alternatively to remove them from circulation, then we could prevent those proteins from being harmful to cells.Misfolded proteins have been implicated in a number of diseases Rosetta Stone Hindi
, including some cancers, as well as ailments related to aging, such as Alzheimer's and Parkinson's diseases.Folding is one of the key steps for the health of the cell, Frydman said.Virtually all proteins have to be folded-some in complex configurations-in order to function properly, and many are known to require a molecule called a chaperone to fold them. Frydman estimates that perhaps 10 percent of the proteins needing chaperones must have one that, like TRiC, is part of the subset called chaperonins. Other work done in Frydman's lab has shown that proteins that have very complex folds seem to require chaperonins.Many of the proteins that have these complex folds are the most important ones for life, Frydman said. The proteins that control the cell cycle, tumor suppressers and the proteins that control the shape of the cell are dependent on chaperonins to get to the folded state.If the chaperones don't work well, then all these proteins that have been made become toxic, she said.TRiC, like all chaperonins, consists of a double-ringed structure that gives it a barrel shape. One ring opens to admit the raw protein into the inner recesses of the folding machine, then closes tightly while, inside the chaperonin black box, the mysteries of molecular origami unfold-or, more correctly, fold. Upon completion of the folding, the ring at the other end opens Rosetta Stone Italian
up to push out the finished product.It is really like a nanomachine. It closes off, the protein is trapped inside and something-we don't understand what-happens inside this chamber, and the protein comes out folded, Frydman said.