High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide
Abstract
In this report we present the high pressure NMR characterization of Aβ42 and two Aβ40 variants with Alzheimer-causing mutations E22G and D23N. While chemical shifts only identified localized changes at ambient pressure compared with Aβ40, high pressure NMR revealed a common site with heightened pressure sensitivity at Q15, K16 and L17 in all three variants, which correlates to higher β-propensity at central hydrophobic cluster (CHC) and faster aggregation.
- Authors:
-
- Rensselaer Polytechnic Institute, Troy, NY (United States)
- Cornell University, Ithaca, NY (United States)
- Rensselaer Polytechnic Institute, Troy, NY (United States); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States). Center for Nonlinear Studies (CNLS)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1994112
- Report Number(s):
- LA-UR-18-21646
Journal ID: ISSN 1359-7345
- Grant/Contract Number:
- 89233218CNA000001
- Resource Type:
- Accepted Manuscript
- Journal Name:
- ChemComm
- Additional Journal Information:
- Journal Volume: 54; Journal Issue: 36; Journal ID: ISSN 1359-7345
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Rosenman, David J., Clemente, Nicolina, Ali, Muhammad, García, Angel Enrique, and Wang, Chunyu. High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide. United States: N. p., 2018.
Web. doi:10.1039/c8cc01674g.
Rosenman, David J., Clemente, Nicolina, Ali, Muhammad, García, Angel Enrique, & Wang, Chunyu. High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide. United States. https://doi.org/10.1039/c8cc01674g
Rosenman, David J., Clemente, Nicolina, Ali, Muhammad, García, Angel Enrique, and Wang, Chunyu. Thu .
"High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide". United States. https://doi.org/10.1039/c8cc01674g. https://www.osti.gov/servlets/purl/1994112.
@article{osti_1994112,
title = {High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide},
author = {Rosenman, David J. and Clemente, Nicolina and Ali, Muhammad and García, Angel Enrique and Wang, Chunyu},
abstractNote = {In this report we present the high pressure NMR characterization of Aβ42 and two Aβ40 variants with Alzheimer-causing mutations E22G and D23N. While chemical shifts only identified localized changes at ambient pressure compared with Aβ40, high pressure NMR revealed a common site with heightened pressure sensitivity at Q15, K16 and L17 in all three variants, which correlates to higher β-propensity at central hydrophobic cluster (CHC) and faster aggregation.},
doi = {10.1039/c8cc01674g},
journal = {ChemComm},
number = 36,
volume = 54,
place = {United States},
year = {Thu Apr 12 00:00:00 EDT 2018},
month = {Thu Apr 12 00:00:00 EDT 2018}
}
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