ArticlePloS one2013
Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- An N-terminal acidic β-sheet domain is responsible for the metal-accumulation properties of amyloid-β protofibrils: a molecular dynamics study.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- Partial Destabilization of Amyloid-β Protofibril by Methionine Photo-Oxidation: A Molecular Dynamic Simulation Study.ACS omega · 2023Article
- Review
- Destabilization of the Alzheimer's amyloid-β peptide by a proline-rich β-sheet breaker peptide: a molecular dynamics simulation study.Journal of molecular modeling · 2021Article
- Destabilization potential of beta sheet breaker peptides on Abeta fibril structure: an insight from molecular dynamics simulation study.RSC advances · 2021Article
- C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape AβACS omega · 2019Article
- Alkali ion influence on structure and stability of fibrillar amyloid-β oligomers.Journal of molecular modeling · 2019Article
- Structural Modulation of Human Amylin Protofilaments by Naturally Occurring Mutations.The journal of physical chemistry. B · 2018Article
- Major Reaction Coordinates Linking Transient Amyloid-β Oligomers to Fibrils Measured at Atomic Level.Biophysical journal · 2017Article
- Theory of amyloid fibril nucleation from folded proteins.Israel journal of chemistry · 2017Article
- Article
- Role of the N-terminus for the stability of an amyloid-β fibril with three-fold symmetry.PloS one · 2017Article
- Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils.The Journal of chemical physics · 2016Article
- Coupling of Zinc-Binding and Secondary Structure in Nonfibrillar Aβ40 Peptide Oligomerization.Journal of chemical information and modeling · 2015Article
- On the lack of polymorphism in Aβ-peptide aggregates derived from patient brains.Protein science : a publication of the Protein Society · 2015Article
- The elusive nature and diagnostics of misfolded Aβ oligomers.Frontiers in chemistry · 2015Review
- Engineering complementary hydrophobic interactions to control β-hairpin peptide self-assembly, network branching, and hydrogel properties.Biomacromolecules · 2014Article
- Stability of Iowa mutant and wild type Aβ-peptide aggregates.The Journal of chemical physics · 2014Article
- The conformational stability of nonfibrillar amyloid-β peptide oligomers critically depends on the C-terminal peptide length.ACS chemical neuroscience · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid-[Formula: see text] (A[Formula: see text]) oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1) elongation of short protofilaments; (2) breakage of large protofilaments; (3) formation of short protofilament pairs; and (4) elongation of protofilament pairs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.