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First major study of mammalian 'disorderly' proteins

Investigators at St. Jude Children's Research Hospital turned up the heat on "disorderly" proteins and confirmed that most of these unruly molecules perform critical functions in the cell. The St. Jude team completed the first large-scale collection, investigation and classification of these so-called intrinsically unstructured proteins (IUPs), a large group of molecules that play vital roles in the daily activities of cells.

The new technique for collecting and identifying IUPs is important because although scientists have been aware of the existence of flexible proteins for many years, they have only recently realized that these molecules play major biological roles in the cell, according to Richard Kriwacki, Ph.D., an associate member of the St. Jude Department of Structural Biology. Moreover, he said, previous work by other researchers suggested that a large proportion of IUPs in mammalian cells play key roles in transmitting signals and coordinating biochemical and genetic activities that keep the cell alive and functioning. Kriwacki is senior author of a report on this work that appears in the prepublication online issue of Journal of Proteome Research.

"Until now there was no way to separate IUPs in large numbers from the more structured proteins and confirm their roles in the cell," Kriwacki said. "Our new technique selectively concentrates the IUPs that are involved in regulating functions in the cell and transmitting signals within them."

Unlike the classic description of proteins described in science textbooks, IUPs are not completely locked into rigid, 3-D shapes that determine their function in the cell. Instead, IUPs have varying amounts of flexibility within their sometimes spaghetti-like structures that is critical for function. For example, one protein named p27 initially looks like a SlinkyTM toy. However, when p27 goes to work, it puts a vise-like grip on an enzyme that otherwise would promote uncontrolle
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Source:St. Jude Children's Research Hospital


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