Intrinsically Disordered Proteins (IDPs) Can Allosterically Control Function Using Principle of “Energetic Frustration” to Simultaneously Tune Transcriptional Activation and Repression;

Proteins carry out almost all processes in living organisms, including moving other molecules from one place to another, replicating DNA, conveying genetic information from genes to cells, controlling immune response, driving metabolism, and building muscle. Not all protein molecules are created equal, however, and some are better understood than others. Now, a team of scientists led by a Johns Hopkins University biologist has cracked a key part of the mystery surrounding a particular group of proteins that emerged as a distinct type less than 30 years ago. The finding, reported on October 12, 2017 in the online journal eLife, could eventually lead to treatments for diseases that range from cancer to neurological disorders. The title of the article is “Genetically Tunable Frustration Controls Allostery in an Intrinsically Disordered Transcription Factor.” Dr. Vincent Hilser, Professor and Chair of the Johns Hopkins Department of Biology, said it's not possible to say when this new research will translate into improved treatments, "but what is clear is understanding how these things work is a critical step toward that." These so-called "intrinsically disordered proteins" (IDPs) do not look like the more familiar type, but they make up about 40 percent of all proteins. Perhaps more importantly, they constitute the majority of proteins involved in the process called "transcription." That's how the instructions in the DNA genetic code are converted to messenger RNA that codes for the production of proteins in the ribosomes. It is not clear exactly how errors in transcription affect human health, but it is known that these errors are involved in most cancers, Dr. Hilser said. "It's probably going to be the case that to understand many, if not most, cancers, you're going to have to understand disorder," he said, meaning disordered proteins.
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