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Intermolecular Structure Determination of Amyloid Fibrils with 2 Magic-Angle Spinning and Dynamic Nuclear Polarization NMR

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dc.contributor.author Bayro, Marvin J.
dc.contributor.author Debelouchina, Galia Tzvetanova
dc.contributor.author Eddy, Matthew Thomas
dc.contributor.author Birkett, Neil R.
dc.contributor.author MacPhee, Catherine E.
dc.contributor.author Rosay, Melanie
dc.contributor.author Maas, Werner E.
dc.contributor.author Dobson, Christopher M.
dc.contributor.author Griffin, Robert Guy
dc.date.accessioned 2012-11-01T20:43:17Z
dc.date.available 2012-11-01T20:43:17Z
dc.date.issued 2011-07
dc.date.submitted 2011-04
dc.identifier.issn 0002-7863
dc.identifier.issn 1520-5126
dc.identifier.uri http://hdl.handle.net/1721.1/74559
dc.description.abstract We describe magic-angle spinning NMR experiments designed to elucidate the interstrand architecture of amyloid fibrils. Three methods are introduced for this purpose, two being based on the analysis of long-range [superscript 13]C–[superscript 13]C correlation spectra and the third based on the identification of intermolecular interactions in [superscript 13]C–[superscript 15]N spectra. We show, in studies of fibrils formed by the 86-residue SH3 domain of PI3 kinase (PI3-SH3 or PI3K-SH3), that efficient [superscript 13]C–[superscript 13]C correlation spectra display a resonance degeneracy that establishes a parallel, in-register alignment of the proteins in the amyloid fibrils. In addition, this degeneracy can be circumvented to yield direct intermolecular constraints. The [superscript 13]C–[superscript 13]C experiments are corroborated by [superscript 15]N–[superscript 13]C correlation spectra obtained from a mixed [[superscript 15]N,[superscript 12]C]/[[superscript 14]N,[superscript 13]C] sample which directly quantify interstrand distances. Furthermore, when the spectra are recorded with signal enhancement provided by dynamic nuclear polarization (DNP) at 100 K, we demonstrate a dramatic increase (from 23 to 52) in the number of intermolecular [superscript 15]N–[superscript 13]C constraints detectable in the spectra. The increase in the information content is due to the enhanced signal intensities and to the fact that dynamic processes, leading to spectral intensity losses, are quenched at low temperatures. Thus, acquisition of low temperature spectra addresses a problem that is frequently encountered in MAS spectra of proteins. In total, the experiments provide 111 intermolecular [superscript 13]C–[superscript 13]C and [superscript 15]N–[superscript 13]C constraints that establish that the PI3-SH3 protein strands are aligned in a parallel, in-register arrangement within the amyloid fibril. en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant EB-003151) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant EB-002804) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant EB-002026) en_US
dc.language.iso en_US
dc.publisher American Chemical Society (ACS) en_US
dc.relation.isversionof http://dx.doi.org/ 10.1021/ja203756x en_US
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. en_US
dc.source Prof. Griffin via Erja Kajosalo en_US
dc.title Intermolecular Structure Determination of Amyloid Fibrils with 2 Magic-Angle Spinning and Dynamic Nuclear Polarization NMR en_US
dc.type Article en_US
dc.identifier.citation Bayro, Marvin J. et al. “Intermolecular Structure Determination of Amyloid Fibrils with Magic-Angle Spinning and Dynamic Nuclear Polarization NMR.” Journal of the American Chemical Society 133.35 (2011): 13967–13974. en_US
dc.contributor.department Francis Bitter National Magnet Laboratory en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Chemistry en_US
dc.contributor.approver Griffin, Robert G.
dc.contributor.mitauthor Bayro, Marvin J.
dc.contributor.mitauthor Debelouchina, Galia Tzvetanova
dc.contributor.mitauthor Eddy, Matthew Thomas
dc.contributor.mitauthor Griffin, Robert Guy
dc.relation.journal Journal of the American Chemical Society en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Author's final manuscript en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Bayro, Marvin J.; Debelouchina, Galia T.; Eddy, Matthew T.; Birkett, Neil R.; MacPhee, Catherine E.; Rosay, Melanie; Maas, Werner E.; Dobson, Christopher M.; Griffin, Robert G. en


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