dc.contributor.author | Debelouchina, Galia Tzvetanova | |
dc.contributor.author | Bayro, Marvin J. | |
dc.contributor.author | Radford, Sheena E. | |
dc.contributor.author | Griffin, Robert Guy | |
dc.contributor.author | Platt, Geoffrey W. | |
dc.date.accessioned | 2012-08-07T18:27:38Z | |
dc.date.available | 2012-08-07T18:27:38Z | |
dc.date.issued | 2010-11 | |
dc.date.submitted | 2010-09 | |
dc.identifier.issn | 0002-7863 | |
dc.identifier.issn | 1520-5126 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/72019 | |
dc.description.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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant no. EB003151) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant no. EB002026) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant no. P41 RR-01081) | en_US |
dc.description.sponsorship | Wellcome Trust (London, England) (grant no. 075675) | en_US |
dc.description.sponsorship | Wellcome Trust (London, England) (grant no. 062164) | en_US |
dc.language.iso | en_US | |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1021/ja107987f | 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 | PMC | en_US |
dc.title | Intermolecular Alignment in Beta 2-Microglobulin Amyloid Fibrils | en_US |
dc.type | Article | en_US |
dc.identifier.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. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.department | Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology) | en_US |
dc.contributor.approver | Griffin, Robert Guy | |
dc.contributor.mitauthor | Debelouchina, Galia Tzvetanova | |
dc.contributor.mitauthor | Bayro, Marvin J. | |
dc.contributor.mitauthor | Griffin, Robert Guy | |
dc.relation.journal | Journal of the American Chemical Society | en_US |
dc.eprint.version | Final published version | 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 | Debelouchina, Galia T.; Platt, Geoffrey W.; Bayro, Marvin J.; Radford, Sheena E.; Griffin, Robert G. | en |
dc.identifier.orcid | https://orcid.org/0000-0003-1589-832X | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |