Accurate Determination of Interstrand Distances and Alignment in Amyloid Fibrils by Magic Angle Spinning NMR
Author(s)
Bajaj, Vikram S.; Caporini, Marc A.; Griffin, Robert Guy; Veshtort, Mikhail; Dobson, Christopher M.; Fitzpatrick, Anthony W.; MacPhee, Cait E.; Vendruscolo, Michele; ... Show more Show less
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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.
Date issued
2010-10Department
Massachusetts Institute of Technology. Department of Chemistry; Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)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
ISSN
1520-6106
1520-5207