30 November 2012
Publication year: 2012 Source:Biochemical and Biophysical Research Communications, Volume 428, Issue 4
Alzheimer’s disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid ?-protein (A?42) in the brain. During the process of fibrillation, the A?42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A?42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A?42 protofibrils was analyzed by 13C–13C rotational resonance experiments in the solid state. Unlike the A?42 fibrils, an intermolecular 13C–13C correlation was not found in the A?42 protofibrils. This result suggests that the ?-strands of the A?42 protofibrils are not in an in-register parallel orientation. A?42 monomers would assemble to form protofibrils with the ?-strand conformation, then transform into fibrils by forming intermolecular parallel ?-sheets. Highlights
? The supramolecular structure of A?42 protofibrils was analyzed by solid-state NMR. ? The Ala-21 residue in the A?42 protofibrils is included in a slightly disordered ?-strand. ? The A?42 protofibrils do not form intermolecular in-register parallel ?-sheets.
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Bioorg Med Chem. 2011 Aug 27;
Authors: Masuda Y, Fukuchi M, Yatagawa T, Tada M, Takeda K, Irie K, Akagi KI, Monobe Y, Imazawa T, Takegoshi K
Abstract
Aggregation of 42-residue amyloid ?-protein (A?42) plays a pivotal role in the etiology of Alzheimer's disease (AD). Curcumin, the yellow pigment in the rhizome of turmeric, attracts...
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09-20-2011 03:10 PM
Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy
Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy
Jonathan J. Helmus, Krystyna Surewicz, Marcin I. Apostol, Witold K. Surewicz and Christopher P. Jaroniec
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja206469q/aop/images/medium/ja-2011-06469q_0003.gif
Journal of the American Chemical Society
DOI: 10.1021/ja206469q
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/e9F1wuu5168
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08-16-2011 03:17 AM
Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.
Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.
Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.
J Am Chem Soc. 2011 Aug 10;
Authors: Helmus JJ, Surewicz K, Apostol MI, Surewicz WK, Jaroniec CP
The Y145Stop mutant of human prion protein, huPrP23-144, has been linked to PrP cerebral amyloid angiopathy, an inherited amyloid disease, and also serves as a valuable in vitro model for investigating the molecular basis of...
Solid-state NMR of amyloid membrane interactions.
Solid-state NMR of amyloid membrane interactions.
Solid-state NMR of amyloid membrane interactions.
Methods Mol Biol. 2011;752:165-77
Authors: Gehman JD, Separovic F
Solid-state NMR pulse sequences often feature fewer pulses and delays than the more common solution NMR experiments. This ostensible simplicity, however, belies the care with which experimental parameters must be determined, as solid-state NMR can be much less forgiving of improper experimental set-up. This is especially true of "semi-solid" samples, such as the phospholipid vesicles...
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06-30-2011 01:24 PM
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Biophys J. 2011 Feb 2;100(3):711-9
Authors: Lu JX, Yau WM, Tycko R
The amyloid precursor protein (APP) is subject to proteolytic processing by ?-secretase within neuronal membranes, leading to Alzheimer's disease-associated ?-amyloid peptide production by cleavage near the midpoint of the*single...
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02-02-2011 12:40 PM
Solid-State NMR Studies of Amyloid Fibril Structure.
Solid-State NMR Studies of Amyloid Fibril Structure.
Solid-State NMR Studies of Amyloid Fibril Structure.
Annu Rev Phys Chem. 2010 Apr 2;
Authors: Tycko R
Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In...
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01-12-2011 11:11 AM
Probing water-accessibility in HET-s(218-289) amyloid fibrils by solid-state NMR.
Probing water-accessibility in HET-s(218-289) amyloid fibrils by solid-state NMR.
Probing water-accessibility in HET-s(218-289) amyloid fibrils by solid-state NMR.
J Mol Biol. 2010 Nov 18;
Authors: Van Melckebeke H, Schanda P, Gath J, Wasmer C, Verel R, Lange A, Meier BH, Böckmann A
Despite its importance in the context of conformational diseases, structural information is still sparse for protein fibrils. Hydrogen/deuterium exchange measurements of backbone amides allow to identify hydrogen-bonding patterns and reveal pertinent information about...
Solid-state NMR analysis of the ?-strand orientation of the protofibrils of amyloid ?-protein
Linear Mode
