Intermolecular Alignment in Beta 2-Microglobulin Amyloid Fibrils
Name
Griffin_Intermolecular Alignment.pdf
Size
405.89 KB
Format
Adobe PDF
Checksum (MD5)
65c1bd616f14fd50db74672b13c8693e
Author(s)
Debelouchina, Galia Tzvetanova
Bayro, Marvin J.
Radford, Sheena E.
Griffin, Robert Guy
Platt, Geoffrey W.
Date Issued
November 2010
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Debelouchina, Galia T. et al. “Intermolecular Alignment in β2-Microglobulin Amyloid Fibrils.” Journal of the American Chemical Society 132.48 (2010): 17077–17079. Copyright 2010 American Chemical Society.
Version
Final published version
Abstract
The deposition of amyloid-like fibrils, composed primarily of the 99-residue protein β2-microglobulin (β2m), is one of the characteristic symptoms of dialysis-related amyloidosis. Fibrils formed in vitro at low pH and low salt concentration share many properties with the disease related fibrils and have been extensively studied by a number of biochemical and biophysical methods. These fibrils contain a significant β-sheet core and have a complex cryoEM electron density profile. Here, we investigate the intrasheet arrangement of the fibrils by means of [superscript 15]N−[superscript 13]C MAS NMR correlation spectroscopy. We utilize a fibril sample grown from a 50:50 mixture of [superscript 15]N,[superscript 12]C- and [superscript 14]N,[superscript 13]C-labeled β2m monomers, the latter prepared using 2-[superscript 13]C glycerol as the carbon source. Together with the use of ZF-TEDOR mixing, this sample allowed us to observe intermolecular [superscript 15]N−[superscript 13]C backbone-to-backbone contacts with excellent resolution and good sensitivity. The results are consistent with a parallel, in-register arrangement of the protein subunits in the fibrils and suggest that a significant structural reorganization occurs from the native to the fibril state.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ja107987f
