Structural Polymorphism of Alzheimer's ?-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study.
J Am Chem Soc. 2016 Jul 14;
Authors: Elkins MR, Wang T, Nick M, Jo H, Lemmin T, Prusiner SB, DeGrado WF, Stoehr J, Hong M
Abstract
The amyloid-? (A?) peptide of the Alzheimer's disease (AD) forms polymorphic fibrils on the micrometer scale and molecular scale. Various fibril growth conditions have been identified to cause polymorphism, but the intrinsic amino acid sequence basis for this polymorphism has been unclear. Several single-site mutations in the center of the A? sequence cause different disease phenotypes and fibrillization properties. The E22G (Arctic) mutant is found in familial AD and forms protofibrils more rapidly than wild-type A?. Here, we use solid-state NMR spectroscopy to investigate the structure, dynamics, hydration and morphology of Arctic E22G A?40 fibrils. 13C, 15N-labeled synthetic E22G A?40 peptides are studied and compared with wild-type and Osaka E22? A?40 fibrils. Under the same fibrillization conditions, Arctic A?40 exhibits a high degree of polymorphism, showing at least four sets of NMR chemical shifts for various residues, while the Osaka and wild-type A?40 fibrils show a single or a predominant set of chemical shifts. Thus, structural polymorphism is intrinsic to the Arctic E22G A?40 sequence. Chemical shifts and inter-residue contacts obtained from 2D correlation spectra indicate that one of the major Arctic conformers has surprisingly high structural similarity with wild-type A?42. 13C-1H dipolar order parameters, 1H rotating-frame spin-lattice relaxation times and water-to-protein spin diffusion experiments reveal substantial differences in the dynamics and hydration of Arctic, Osaka and wild-type A?40 fibrils. Together, these results strongly suggest that electrostatic interactions in the center of the A? peptide sequence play a crucial role in the three-dimensional fold of the fibrils, and by inference, fibril-induced neuronal toxicity and AD pathogenesis.
PMID: 27414264 [PubMed - as supplied by publisher]
Structural Insight into an Alzheimer’s Brain-Derived Spherical Assembly of Amyloid ? by Solid-State NMR
Structural Insight into an Alzheimer’s Brain-Derived Spherical Assembly of Amyloid ? by Solid-State NMR
Sudhakar Parthasarathy, Masafumi Inoue, Yiling Xiao, Yoshitaka Matsumura, Yo-ichi Nabeshima, Minako Hoshi and Yoshitaka Ishii
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/jacs.5b03373/20150518/images/medium/ja-2015-03373k_0004.gif
Journal of the American Chemical Society
DOI: 10.1021/jacs.5b03373
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/IQmUqF-Pq1k
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[NMR paper] Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.
Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.
Related Articles Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.
J Am Chem Soc. 2015 May 4;
Authors: Parthasarathy S, Inoue M, Xiao Y, Matsumura Y, Nabeshima YI, Hoshi M, Ishii Y
Abstract
Accumulating evidence suggests that various neurodegenerative diseases, including Alzheimer's disease (AD), are linked to cytotoxic diffusible aggregates of amyloid proteins, which are...
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05-06-2015 11:59 AM
[NMR paper] Capturing a reactive state of amyloid aggregates: NMR-based characterization of copper-bound Alzheimer disease amyloid ?-fibrils in a redox cycle.
Capturing a reactive state of amyloid aggregates: NMR-based characterization of copper-bound Alzheimer disease amyloid ?-fibrils in a redox cycle.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jbc_final.gif Related Articles Capturing a reactive state of amyloid aggregates: NMR-based characterization of copper-bound Alzheimer disease amyloid ?-fibrils in a redox cycle.
J Biol Chem. 2014 Apr 4;289(14):9998-10010
Authors: Parthasarathy S, Yoo B, McElheny D, Tay W,...
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[NMR paper] Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-? peptide: perspectives for DNP.
Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-? peptide: perspectives for DNP.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-? peptide: perspectives for DNP.
J Biomol NMR. 2013 Aug;56(4):359-63
Authors: Lopez del Amo JM, Schneider D, Loquet A, Lange A, Reif B
Abstract
Dynamic Nuclear Polarization solid-state NMR...
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Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-beta peptide: perspectives for DNP
From The DNP-NMR Blog:
Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-beta peptide: perspectives for DNP
Lopez Del Amo, J.M., et al., Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-beta peptide: perspectives for DNP. J Biomol NMR, 2013: p. 1-5.
http://www.ncbi.nlm.nih.gov/pubmed/23793606
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Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-beta peptide: perspectives for DNP
From The DNP-NMR Blog:
Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-beta peptide: perspectives for DNP
Lopez del Amo, J.-M., et al., Cryogenic solid state NMR studies of fibrils of the Alzheimer’s disease amyloid-? peptide: perspectives for DNP. J. Biomol. NMR, 2013: p. 1-5.
http://www.ncbi.nlm.nih.gov/pubmed/23793606
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07-19-2013 09:20 PM
[NMR paper] Hydrogen bonding in Alzheimer's amyloid-? fibrils probed by 15N{17O} REAPDOR solid-state NMR spectroscopy.
Hydrogen bonding in Alzheimer's amyloid-? fibrils probed by 15N{17O} REAPDOR solid-state NMR spectroscopy.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles Hydrogen bonding in Alzheimer's amyloid-? fibrils probed by 15N{17O} REAPDOR solid-state NMR spectroscopy.
Angew Chem Int Ed Engl. 2012 Oct 8;51(41):10289-92
Authors: Antzutkin ON, Iuga D, Filippov AV, Kelly RT, Becker-Baldus J, Brown SP, Dupree R
PMID: 22976560
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Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer’s ? by Solid-State NMR Spectroscopy
Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer’s ? by Solid-State NMR Spectroscopy
Sudhakar Parthasarathy, Fei Long, Yifat Miller, Yiling Xiao, Dan McElheny, Kent Thurber, Buyong Ma, Ruth Nussinov and Yoshitaka Ishii
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja1072178/aop/images/medium/ja-2010-072178_0006.gif
Journal of the American Chemical Society
DOI: 10.1021/ja1072178
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