Mechanisms of protein secretion and protein folding in baker's yeast

What is it about?

All cells produce proteins that carry out essential chemical activities. Some of these are retained inside the cells, but others are secreted into the surrounding medium. In eukaryotes like animals, plants and fungi, secretion involves processing by a specialised protein folding machinery that helps the secreted proteins adopt their final fold and thereby achieve their full chemical activity. This folding process involves the transfer of electrons from the folded proteins to molecular oxygen, and is hence termed "oxidative folding". In this study we generated detailed biochemical data on reconstituted oxidative folding pathway in test tubes, which we then used in conjunction with computer models to make quantitative predictions of how this pathway behaves in yeast cells (a commonly used model organism for studying the general biology of eukaryotic cells).

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Why is it important?

Many modern drugs are proteins, and are produced recombinantly ie by introducing additional genetic material into host cells. Recombinant genes in baker's yeast are currently used to produce insulin for the treatment of diabetes, human serum albumin for the treatment of burns and blood loss and as a general ingredient in pharmaceutical preparations, and vaccines against hepatitis B, human papillomavirus and other infectious agents. By studying the capacity of the cellular machinery that produces such recombinant proteins, we were able to make recommendations for the design of improved production strains of yeast that produce proteins of interest more efficiently.

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