Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Structural characterization of E22G Aβ1-42 fibrils via1H detected MAS NMR

Golota, Natalie C. ; Michael, Brian ; Saliba, Edward P. ; Linse, Sara LU and Griffin, Robert G. (2024) In Physical Chemistry Chemical Physics
Abstract

Amyloid fibrils have been implicated in the pathogenesis of several neurodegenerative diseases, the most prevalent example being Alzheimer's disease (AD). Despite the prevalence of AD, relatively little is known about the structure of the associated amyloid fibrils. This has motivated our studies of fibril structures, extended here to the familial Arctic mutant of Aβ1-42, E22G-Aβ1-42. We found E22G-AβM0,1-42 is toxic to Escherichia coli, thus we expressed E22G-Aβ1-42 fused to the self-cleavable tag NPro in the form of its EDDIE mutant. Since the high surface activity of E22G-Aβ1-42 makes it difficult to obtain more than sparse quantities of fibrils, we employed... (More)

Amyloid fibrils have been implicated in the pathogenesis of several neurodegenerative diseases, the most prevalent example being Alzheimer's disease (AD). Despite the prevalence of AD, relatively little is known about the structure of the associated amyloid fibrils. This has motivated our studies of fibril structures, extended here to the familial Arctic mutant of Aβ1-42, E22G-Aβ1-42. We found E22G-AβM0,1-42 is toxic to Escherichia coli, thus we expressed E22G-Aβ1-42 fused to the self-cleavable tag NPro in the form of its EDDIE mutant. Since the high surface activity of E22G-Aβ1-42 makes it difficult to obtain more than sparse quantities of fibrils, we employed 1H detected magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments to characterize the protein. The 1H detected 13C-13C methods were first validated by application to fully protonated amyloidogenic nanocrystals of GNNQQNY, and then applied to fibrils of the Arctic mutant of Aβ, E22G-Aβ1-42. The MAS NMR spectra indicate that the biosynthetic samples of E22G-Aβ1-42 fibrils comprise a single conformation with 13C chemical shifts extracted from hCH, hNH, and hCCH spectra that are very similar to those of wild type Aβ1-42 fibrils.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
in press
subject
in
Physical Chemistry Chemical Physics
publisher
Royal Society of Chemistry
external identifiers
  • pmid:38715538
  • scopus:85192984364
ISSN
1463-9076
DOI
10.1039/d4cp00553h
language
English
LU publication?
yes
id
999a3023-8e39-4cf3-af02-df6c3681b9bc
date added to LUP
2024-05-23 11:13:37
date last changed
2024-06-06 12:12:20
@article{999a3023-8e39-4cf3-af02-df6c3681b9bc,
  abstract     = {{<p>Amyloid fibrils have been implicated in the pathogenesis of several neurodegenerative diseases, the most prevalent example being Alzheimer's disease (AD). Despite the prevalence of AD, relatively little is known about the structure of the associated amyloid fibrils. This has motivated our studies of fibril structures, extended here to the familial Arctic mutant of Aβ<sub>1-42</sub>, E22G-Aβ<sub>1-42</sub>. We found E22G-Aβ<sub>M0,1-42</sub> is toxic to Escherichia coli, thus we expressed E22G-Aβ<sub>1-42</sub> fused to the self-cleavable tag N<sup>Pro</sup> in the form of its EDDIE mutant. Since the high surface activity of E22G-Aβ<sub>1-42</sub> makes it difficult to obtain more than sparse quantities of fibrils, we employed <sup>1</sup>H detected magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments to characterize the protein. The <sup>1</sup>H detected <sup>13</sup>C-<sup>13</sup>C methods were first validated by application to fully protonated amyloidogenic nanocrystals of GNNQQNY, and then applied to fibrils of the Arctic mutant of Aβ, E22G-Aβ<sub>1-42</sub>. The MAS NMR spectra indicate that the biosynthetic samples of E22G-Aβ<sub>1-42</sub> fibrils comprise a single conformation with <sup>13</sup>C chemical shifts extracted from hCH, hNH, and hCCH spectra that are very similar to those of wild type Aβ<sub>1-42</sub> fibrils.</p>}},
  author       = {{Golota, Natalie C. and Michael, Brian and Saliba, Edward P. and Linse, Sara and Griffin, Robert G.}},
  issn         = {{1463-9076}},
  language     = {{eng}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Physical Chemistry Chemical Physics}},
  title        = {{Structural characterization of E22G Aβ<sub>1-42</sub> fibrils via<sup>1</sup>H detected MAS NMR}},
  url          = {{http://dx.doi.org/10.1039/d4cp00553h}},
  doi          = {{10.1039/d4cp00553h}},
  year         = {{2024}},
}