This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloid fibers are formed when normally soluble proteins change conformation to form insoluble filaments that can cause severe damage and even death. Amyloidoses include Alzheimer?s disease, type II diabetes, hereditary amyloidoses, and a variety of prion diseases including Creutzfeldt-Jakob disease, BSE (?mad cow disease?), and scrapie. Mammalian prions are infections protein aggregates formed by the prion protein PrP when it folds into aberrant structures. Amyloids ? by definition ? share a cross-beta structure, but the structural details are not known. Amyloid fibers have resisted characterization by crystallography and NMR. Fiber diffraction is an effective method for determining the structural details of filamentous assemblies, and in combination with electron microscopy offers the best hope for elucidating the structures of prions and other amyloids. Structural studies are needed to answer fundamental protein folding questions, to understand the process of amyloid formation, and for rational drug design. We use very small quantities of material to make oriented sols and dried fibers in high magnetic fields under controlled conditions. Magnetic fields have been shown to assist amyloid orientation. Synthetic prions have opened up new possibilities of obtaining material. Improved prion availability, improved methods of specimen preparation, and intense, high quality synchrotron radiation together offer an unprecedented opportunity to obtain improved amyloid diffraction data.
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