ArticleACS chemical neuroscience2021
Pulsed Hydrogen-Deuterium Exchange Reveals Altered Structures and Mechanisms in the Aggregation of Familial Alzheimer's Disease Mutants.
Article in ACS chemical neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Tau4RD fibril polymorphism is imprinted during early aggregation.bioRxiv : the preprint server for biology · 2025Article
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
- Microgravity-Assisted Exploration of the Conformational Space of Amyloid β Affected by Tottori-Type Familial Mutation D7N.ACS chemical neuroscience · 2025Article
- Mass-Spectrometry-Based GEE Footprinting Characterizes Kinetic Mechanisms and Sites of Conformational Change in Amyloid β 1-42 Aggregation.ACS chemical neuroscience · 2025Article
- Generating the polymorph landscapes of amyloid fibrils using AI: RibbonFold.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mass Spectrometry-Based Protein Footprinting for Protein Structure Characterization.Accounts of chemical research · 2025Article
- Exploration of Resveratrol as a Potent Modulator of α-Synuclein Fibril Formation.ACS chemical neuroscience · 2024Article
- Biochemical and hydrogen-deuterium exchange studies of the single nucleotide polymorphism Y649C in human platelet 12-lipoxygenase linked to a bleeding disorder.Archives of biochemistry and biophysics · 2023Article
- An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation.Nature communications · 2022Article
- Neglected N-Truncated Amyloid-β Peptide and Its Mixed Cu-Zn Complexes.The protein journal · 2022Review
- Characterizing Endogenous Protein Complexes with Biological Mass Spectrometry.Chemical reviews · 2022Review
- Using mass spectrometry-based methods to understand amyloid formation and inhibition of alpha-synuclein and amyloid beta.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations of the Amyloid Precursor Protein, from which the amyloid β peptide Aβ42 is cleaved, are associated with familial Alzheimer's disease. The disease-relevant familial mutations include the Arctic (E22G), Iowa (D23N), Italian (E22K), Dutch (E22Q), Japanese (D7N), English (D6R), and Flemish (A21G) variants. A detailed mechanistic understanding of the aggregation behavior of the mutant peptides at the residue level is, however, still lacking. We report here a study of the aggregation kinetics of these mutants in vitro by pulsed hydrogen-deuterium exchange mass spectrometry (HDX-MS) to obtain a temporally and sequence resolved picture of their self-assembly. For all variants, HDX occurs to give a bimodal distribution representing two soluble classes of aggregates, one protected and one solvent-exposed. There is no evidence of other classes of structural intermediates within the detection limits of the HDX approach. The fractional changes in the bimodal exchange profiles for several regions of Aβ42 reveal that the central and C-terminal peptides gain protection upon fibril formation, whereas the N-terminal regions remain largely solvent-accessible. For these mutants, all peptide fragments follow the same kinetics, acquiring solvent protection at the same time, further supporting that there are no significant populations of intermediate species under our experimental conditions. The results demonstrate the potential of pulsed HDX-MS for resolving the region-specific aggregation behavior of Aβ42 isoforms in solution where X-ray crystallography and solid-state NMR (ssNMR) are challenged.
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