High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide

Rosenman, David J.; Clemente, Nicolina; Ali, Muhammad; García, Angel Enrique; Wang, Chunyu

doi:10.1039/c8cc01674g

Title: 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:

Rosenman, David J. ^[1]; Clemente, Nicolina ^[1]; Ali, Muhammad ^[2];

^[3];

^[1]

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:: Thu Apr 12 00:00:00 EDT 2018

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.

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                    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

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                    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.

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@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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Title: High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide

Abstract

Citation Formats

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An Account of Amyloid Oligomers: Facts and Figures Obtained from Experiments and Simulations journal, March 2016

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A Hexameric Peptide Barrel as Building Block of Amyloid-β Protofibrils journal, September 2014

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Characterization of Aβ Monomers through the Convergence of Ensemble Properties among Simulations with Multiple Force Fields journal, December 2015

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Solution NMR Studies of the Aβ(1−40) and Aβ(1−42) Peptides Establish that the Met35 Oxidation State Affects the Mechanism of Amyloid Formation journal, January 2004

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journal, January 2006

Observation of metastable Aβ amyloid protofibrils by atomic force microscopy
journal, January 1997

The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease
journal, May 1993

A Hexameric Peptide Barrel as Building Block of Amyloid-β Protofibrils
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journal, April 2010

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journal, December 2015

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journal, February 2001

Point Substitution in the Central Hydrophobic Cluster of a Human β-Amyloid Congener Disrupts Peptide Folding and Abolishes Plaque Competence
journal, January 1996

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journal, January 2004

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journal, January 2012

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journal, February 1996

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journal, February 2006

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Molecular structural basis for polymorphism in Alzheimer's -amyloid fibrils
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journal, December 1992

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journal, November 2005

Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.
journal, December 1994

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journal, March 2002

Atomic Resolution Structure of Monomorphic Aβ ₄₂ Amyloid Fibrils
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A New Structural Model of Aβ ₄₀ Fibrils
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journal, August 2001

Ring current effects in the conformation dependent NMR chemical shifts of aliphatic protons in the basic pancreatic trypsin inhibitor
journal, February 1979

Amyloid -protein (A ) assembly: A 40 and A 42 oligomerize through distinct pathways
journal, December 2002

Impact of Hydrostatic Pressure on an Intrinsically Disordered Protein: A High-Pressure NMR Study of α-Synuclein
journal, June 2013

Soluble pool of A? amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease
journal, December 1999

Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease
journal, May 2015

Familial Alzheimer’s Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-β Peptide
journal, February 2017

Oligomerization and Toxicity of β-Amyloid-42 Implicated in Alzheimer's Disease
journal, July 2000

Aβ Monomers Transiently Sample Oligomer and Fibril-Like Configurations: Ensemble Characterization Using a Combined MD/NMR Approach
journal, September 2013

An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp ₇₁₇ ) Mutants
journal, May 1994

Pressure Dependence of 15N Chemical Shifts in Model Peptides Ac-Gly-Gly-X-Ala-NH2
journal, September 2012

Image analysis of β-amyloid load in Alzheimer's disease and relation to dementia severity
journal, December 1995

Distinct Conformational States of the Alzheimer β-Amyloid Peptide Can Be Detected by High-Pressure NMR Spectroscopy
journal, July 2013

Transmembrane Structures for Alzheimer’s Aβ ₁₋₄₂ Oligomers
journal, September 2010

Iowa Variant of Familial Alzheimer’s Disease
journal, April 2010

The Recombinant Amyloid-β Peptide Aβ1–42 Aggregates Faster and Is More Neurotoxic than Synthetic Aβ1–42
journal, February 2010