Accurate Determination of Interstrand Distances and Alignment in Amyloid Fibrils by Magic Angle Spinning NMR
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Griffin_Accurate Determination.pdf
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Author(s)
Bajaj, Vikram S.
Caporini, Marc A.
Griffin, Robert Guy
Veshtort, Mikhail
Dobson, Christopher M.
Fitzpatrick, Anthony W.
MacPhee, Cait E.
Vendruscolo, Michele
Date Issued
October 2010
Journal
Journal of Physical Chemistry B
Publisher
American Chemical Society (ACS)
Citation
Caporini, 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 ACS
Version
Author's final manuscript
Abstract
Amyloid 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
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DOI of Published Version
https://doi.org/10.1021/jp106675h
