ArticleThe Journal of biological chemistry2011
Polymorphic triple beta-sheet structures contribute to amide hydrogen/deuterium (H/D) exchange protection in the Alzheimer amyloid beta42 peptide.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- A turn for the worse: Aβ β-hairpins in Alzheimer's disease.Bioorganic & medicinal chemistry · 2024Review
- Interpreting Hydrogen-Deuterium Exchange Experiments with Molecular Simulations: Tutorials and Applications of the HDXer Ensemble Reweighting Software [Article v1.0].Living journal of computational molecular science · 2021Article
- Interpretation of HDX Data by Maximum-Entropy Reweighting of Simulated Structural Ensembles.Biophysical journal · 2020Article
- Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates.PloS one · 2020Article
- POPPeT: a New Method to Predict the Protection Factor of Backbone Amide Hydrogens.Journal of the American Society for Mass Spectrometry · 2019Article
- Interpreting Hydrogen-Deuterium Exchange Events in Proteins Using Atomistic Simulations: Case Studies on Regulators of G-Protein Signaling Proteins.The journal of physical chemistry. B · 2018Article
- Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data.Frontiers in molecular biosciences · 2017Article
- Role of the N-terminus for the stability of an amyloid-β fibril with three-fold symmetry.PloS one · 2017Article
- Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes.Biochimica et biophysica acta · 2016Review
- A new structural model of Alzheimer's Aβ42 fibrils based on electron paramagnetic resonance data and Rosetta modeling.Journal of structural biology · 2016Article
- Structure of ring-shaped Aβ₄₂ oligomers determined by conformational selection.Scientific reports · 2016Article
- Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease.Physical chemistry chemical physics : PCCP · 2016Article
- Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis.Journal of chemical information and modeling · 2015Article
- Aβ(1-42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease.Nature structural & molecular biology · 2015Article
- Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies.Chemical reviews · 2015Review
- Alzheimer's protective A2T mutation changes the conformational landscape of the Aβ₁₋₄₂ monomer differently than does the A2V mutation.Biophysical journal · 2015Article
- Antiparallel triple-strand architecture for prefibrillar Aβ42 oligomers.The Journal of biological chemistry · 2014Article
- Structural insights into Aβ42 oligomers using site-directed spin labeling.The Journal of biological chemistry · 2013Article
- Selective molecular recognition in amyloid growth and transmission and cross-species barriers.Journal of molecular biology · 2012Review
- Combining H/D exchange mass spectroscopy and computational docking reveals extended DNA-binding surface on uracil-DNA glycosylase.Nucleic acids research · 2012Article
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2 authors.
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Abstract
Characterization of the polymorphic structural range of Aβ oligomers is important to the understanding of the mechanisms of toxicity. Yet for highly polymorphic ensembles, experimental structural elucidation is difficult. Here, we use a combination of NMR solvent protection experiments and computational structural screening to identify major species in the amyloid conformational ensemble. We examined the polymorphic pentamer and fibril seeds of Aβ42 and its mutants and compared the theoretical backbone amide protection obtained from simulations with experimental hydrogen/deuterium (H/D) exchange protection ratio. We observed that highly flexible pentamers do not share structural similarities with fibril seed oligomers, except the turn regions. We found that a novel amyloid structural motif of a triple β-sheet, with the N-terminal residues interacting with the core (Lys(17)-Glu(22)) β-sheet region, correlates with H/D exchange protection. The triple β-sheet Aβ42 oligomer has a minimal exposure of hydrophobic residues and is further stabilized by the E22Q (Dutch) mutation in Alzheimer disease. The experimental H/D exchange solvent protection ratio implies that triple β-sheet fibrils and globulomers could coexist in the Aβ42 ensemble, pointing to a broad heterogeneous aggregate population. Our results suggest that an approach that combines computational modeling with NMR protection data can be a useful strategy for obtaining clues to the preferred conformational species of the assemblies in solution and help in alleviating experimental difficulties and consequently possible errors in the exchange data for Aβ42 fibrils.
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