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dc.contributor.authorBajaj, Vikram S.
dc.contributor.authorCaporini, Marc A.
dc.contributor.authorGriffin, Robert Guy
dc.contributor.authorVeshtort, Mikhail
dc.contributor.authorDobson, Christopher M.
dc.contributor.authorFitzpatrick, Anthony W.
dc.contributor.authorMacPhee, Cait E.
dc.contributor.authorVendruscolo, Michele
dc.date.accessioned2012-09-25T13:15:38Z
dc.date.available2012-09-25T13:15:38Z
dc.date.issued2010-10
dc.date.submitted2010-09
dc.identifier.issn1520-6106
dc.identifier.issn1520-5207
dc.identifier.urihttp://hdl.handle.net/1721.1/73155
dc.description.abstractAmyloid fibrils are structurally ordered aggregates of proteins whose formation is associated with many neurodegenerative and other diseases. For that reason, their high-resolution structures are of considerable interest and have been studied using a wide range of techniques, notably electron microscopy, X-ray diffraction, and magic angle spinning (MAS) NMR. Because of the excellent resolution in the spectra, MAS NMR is uniquely capable of delivering site-specific, atomic resolution information about all levels of amyloid structure: (1) the monomer, which packs into several (2) protofilaments that in turn associate to form a (3) fibril. Building upon our high-resolution structure of the monomer of an amyloid-forming peptide from transthyretin (TTR105−115), we introduce single 1-13C labeled amino acids at seven different sites in the peptide and measure intermolecular carbonyl−carbonyl distances with an accuracy of 0.11 A. Our results conclusively establish a parallel, in register, topology for the packing of this peptide into a β-sheet and provide constraints essential for the determination of an atomic resolution structure of the fibril. Furthermore, the approach we employ, based on a combination of a double-quantum filtered variant of the DRAWS recoupling sequence and multispin numerical simulations in SPINEVOLUTION, is general and should be applicable to a wide range of systems.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant no. EB-002026)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant no. EB003151)en_US
dc.description.sponsorshipLeverhulme Trusten_US
dc.description.sponsorshipWellcome Trust (London, England)en_US
dc.description.sponsorshipEngineering and Physical Sciences Research Councilen_US
dc.description.sponsorshipRoyal Society (Great Britain)en_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada (NSERC)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/jp106675hen_US
dc.rightsArticle 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.sourcePMCen_US
dc.titleAccurate Determination of Interstrand Distances and Alignment in Amyloid Fibrils by Magic Angle Spinning NMRen_US
dc.typeArticleen_US
dc.identifier.citationCaporini, Marc A. et al. “Accurate Determination of Interstrand Distances and Alignment in Amyloid Fibrils by Magic Angle Spinning NMR.” The Journal of Physical Chemistry B 114.42 (2010): 13555–13561. (c) 2010 ACSen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.departmentFrancis Bitter Magnet Laboratory (Massachusetts Institute of Technology)en_US
dc.contributor.mitauthorBajaj, Vikram S.
dc.contributor.mitauthorCaporini, Marc A.
dc.contributor.mitauthorGriffin, Robert Guy
dc.contributor.mitauthorVeshtort, Mikhail
dc.relation.journalJournal of Physical Chemistry Ben_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCaporini, Marc A.; Bajaj, Vikram S.; Veshtort, Mikhail; Fitzpatrick, Anthony; MacPhee, Cait E.; Vendruscolo, Michele; Dobson, Christopher M.; Griffin, Robert G.en
dc.identifier.orcidhttps://orcid.org/0000-0003-1589-832X
mit.licensePUBLISHER_POLICYen_US


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