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Exploring solid-state 17O NMR to distinguish secondary structures in Alzheimer's Aβ fibrils
Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.ORCID iD: 0000-0003-1067-7990
University of Warwick.
University of Warwick.
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2009 (English)In: Euromar 2009: Magnetics Resonance Conference, 5-9 July 2009, Göteborg, Sweden. Programme and Abstract Book, 2009, 107- p.Conference paper, Meeting abstract (Other academic)
Abstract [en]

It has been shown by a large number of studies that Alzheimer's disease (AD) amyloid-β-peptide (Aβ) deposits contribute directly to the disease's progressive neurodegeneration. Aggregation cascade for Aβ peptides, its relevance to neurotoxicity in the course of AD, various factors modulating Aβ aggregation kinetics and experimental methods useful for these studies were recently discussed [1]. Results of Tycko and co-workers point at neurotoxicity in vitro of the two different types of Alzheimer's amyloid fibrils dispersed by ultrasonication into small fragments [2]. The high toxicity of Aβ oligomers in vitro has been discussed by Stege et. al who have found that the molecular chaperone αB-crystallin prevents Aβ from forming amyloid fibrils but nevertheless enhances Aβ toxicity [3]. Glabe and co-workes successfully prepared antibodies for Aβ oligomers and small spherical aggregates using nanogold technology [4]. They also have shown that these antibodies decrease toxicity of Aβ for SH-SY5Y human neuroblastoma cell cultures in vitro [4]. In this concern both structure of Aβ-oligomers/fibrils and the specific  interaction (aggregation/fusion) of Aβ peptides with nerve cell membranes is of a particular importance [5].We explore Solid-State 17O NMR on selectively 17O,13C,15N-labeled Aβ(1-40), Aβ(11-25) and Ac-Aβ(16-22)-NH2 peptides to distinguish a parallel and anti-parallel β-sheet secondary structures in β-NH2 peptides to distinguish a parallel and anti-parallel β-sheet secondary structures in amyloid fibrils. Aβ(1-40) fibrils form in-registry parallel β-sheets [6], while Aβ(11-25) [7] and Ac-Aβ(16-22)-NH2 [8] form different anti-parallel β-sheet structures, which were previously identified β-NH2 [8] form different anti-parallel β-sheet structures, which were previously identified by 13C multiple-quantum and 13C{15N} REDOR solid-state NMR. In our unpublished work presented here it was found that 17O NMR chemical shifts are sensitive to the type of the secondary structure, i. e. a parallel vs. an anti-parallel β-sheet structures, while the quadrupolar parameters of 17O nuclei unexpectedly do not vary beyond the error limits in the simulated lineshapes of both fibrillized and unfibrillized peptide systems. Results of more advanced solidstate NMR techniques to measure heteronuclear distances, 15N{17O}-REAPDOR, 15N{17O}-TRAPDOR and 17O{15N}-REDOR on selectively 17O-Val18 and 15N-Phe20 labeled Ac-Aβ(16-22)-NH2 fibrils will be also discussed. These novel solid-state NMR experiments will provide additional tools for measuring hydrogen bonding in different secondary structures of peptides in amyloid fibrils.[1.] O.N.Antzutkin, Magn. Reson. Chem. 42 (2004) 231-246; [2.] A.Petkova et al. Science 307 (2005) 262-265; [3.] G.J.J.Stege, et al. Biochem. Biophys. Res. Comm., 262 (1999) 152-156;[4.] R.Kayed et al. Science, 300 (2003) 486-489; [5.] M.Bokvist, et al. J. Mol. Biol. 335 (2004) 1039-1049; [6.] O.N. Antzutkin, et al. Proc. Nat. Acad. Sci, U.S.A., 97 (2000) 13045-13050;[7.] A.T. Petkova, et al. J. Mol. Biol., 335 (2004) 247-260;[8.] J.J. Balbach, Y. (2000) 13045-13050; [9] A.T. Petkova, (2004) 247-260; [10] J.J. Balbach, Y.Ishii, O.N. Antzutkin, et al. Biochemistry 39 (2000) 13748-13759.

Place, publisher, year, edition, pages
2009. 107- p.
Research subject
Chemistry of Interfaces
URN: urn:nbn:se:ltu:diva-34787Local ID: 912fcae0-93ac-11de-8da0-000ea68e967bOAI: diva2:1008038
Euromar 2009, Magnetic Resonance Conference : 05/07/2009 - 09/07/2009
Godkänd; 2009; 20090828 (ysko)Available from: 2016-09-30 Created: 2016-09-30 Last updated: 2017-01-19Bibliographically approved

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