Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.
Keh-Ming Pan,Michael J. Baldwin,J Nguyen,María Gasset,Ana Serban,Darlene Groth,Ingrid Mehlhorn,Ziwei Huang,Robert J. Fletterick,Fred E. Cohen +9 more
TLDR
It is argued that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, and it is likely that this conformational transition is a fundamental event in the propagation of prions.Abstract:
Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were confirmed by circular dichroism measurements. In contrast, the beta-sheet content of PrPSc was 43% and the alpha-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPSc derived by limited proteolysis, designated PrP 27-30, has an even higher beta-sheet content (54%) and a lower alpha-helix content (21%). Neither PrPC nor PrPSc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing findings argue that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, we cannot eliminate the possibility that an undetected chemical modification of a small fraction of PrPSc initiates this process. Since PrPSc seems to be the only component of the "infectious" prion particle, it is likely that this conformational transition is a fundamental event in the propagation of prions.read more
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Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.
Peter E. Wright,H. Jane Dyson +1 more
TL;DR: Many proteins that lack intrinsic globular structure under physiological conditions have now been recognized, and it appears likely that their rapid turnover, aided by their unstructured nature in the unbound state, provides a level of control that allows rapid and accurate responses of the cell to changing environmental conditions.
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Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD
TL;DR: Strain characteristics revealed here suggest that the prion protein may itself encode disease phenotype, consistent with BSE being the source of this new disease.
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Common core structure of amyloid fibrils by synchrotron X-ray diffraction.
TL;DR: Using intense synchrotron sources, it is observed that six different ex vivo amyloid fibrils and two synthetic fibril preparations all gave similar high-resolution X-ray fibre diffraction patterns, consistent with a helical array of beta-sheets parallel to the fibre long axis, with the strands perpendicular to this axis, which confirms that amyloidsfibrils comprise a structural superfamily and share a common protofilament substructure.
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Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials
TL;DR: This review focuses on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators.
References
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Journal Article
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The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Jie Kang,H. G. Lemaire,A. Unterbeck,J. M. Salbaum,Colin L. Masters,K.-H. Grzeschik,Gerd Multhaup,Konrad Beyreuther,Benno Müller-Hill +8 more
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