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ePaper created 2014-10-06, 17:11:00 | version 1.33.00
SRP and the signal sequence of the growing chain of a secretory protein at the tunnel exit of the large ribosomal subunit. “We asked ourselves what happens when the signal sequence of a secretory protein exhibits mutations, preventing SRP from binding,” says Dr. Marco Chiabudini from Rospert’s research group. Previously, one would have assumed that the proteasome now steps in and disposes of the misfolded protein in its role as the cell’s own waste disposal system. However, the researchers discovered that the cell identifies the malformation before the disposal problem arises. “The cellular control machine has no means of identifying the mRNA of a mutated secretory protein,” says Rospert. Only the mutated protein itself no longer conforms to the standard. “What’s new about our findings is that we found a mechanism that recognizes the mutation in the protein early on.” The molecular biologists suspect that this is a general mechanism that is at work in all secretory proteins. To explain their reasoning, Rospert uses the analogy of a bakery with a defective cookie cutter that cuts out hundreds of cookies in the shape of a three-leaf clover rather than the usual four-leaf clover. “Wouldn’t it be wiser to replace the cookie cutter than to go on producing clovers with the wrong number of leaves and throwing them out?” In any case, the cell uses this mechanism to make sure that no defective proteins are produced – the right decision for quality control. “To our surprise, the defective mRNA with the mutated signal sequence was not translated further,” says Rospert. “Therefore, there had to be a previously unknown link between the mRNA and the cell’s quality control system.” If it weren’t for this trick, the defective protein would be synthesized again and again and thrown into the cell’s own waste bin. “The first one of course lands in the trash, but no new ones are produced.” In several further experiments on human cell lines, the scientists found out that a particular 34 Images of the endoplasmic reticulum (ER) and the cell nucleus of yeast cells through a fluorescence microscope: Researchers use fluorescent dyes to reveal the precise localization of proteins and organelles in the cell. In these images, the ER is highlighted by means of a red fluorescent fusion protein, and the deoxyribonucleic acid (DNA) in the cell nucleus is marked with a blue fluorescent dye. Photos: Sachiko Hayashi The Freiburg researchers use dishes with a culture medium to obtain entire colonies of genetically identical cells from a single yeast cell. They use them to determine which factors are involved in the production of proteins. Photo: Patrick Seeger