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    Richard Kriwacki, PhD, and Charles Galea, PhD

    First major study of mammalian "disorderly" proteins

    St. Jude technique for producing cell extracts will help lead to studies of the roles these molecules play in both normal functions and in disease

    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, PhD, 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.

    Based on their studies, the investigators were able to classify all proteins into one of three categories: IUPs, intrinsically folded proteins (IFPs, i.e., fully folded into specific shapes); or mixed ordered or disordered proteins (MPs), which have both structured and unstructured parts.

    “This work further illustrates that the disorderliness of IUPs isn’t just a curiosity,” said Charles Galea, PhD, a postdoctoral fellow in Kriwacki’s lab. “This characteristic is a fundamental part of how these proteins work. So determining their exact nature, including the parts that are disordered, is an important part of understanding how they work in health and disease.” The paper’s first author, Galea, did much of the work on this project.

    Other authors of this study include Vishwajeeth Pagala, John Obenauer, Cheon-Gil Park and Clive Slaughter, also of St. Jude. This work was supported in part by ALSAC, the National Cancer Institute and a Cancer Center (CORE) Support Grant.

    November 2006