ArticleBiophysical journal2020
Edge Strand Dissociation and Conformational Changes in Transthyretin under Amyloidogenic Conditions.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Correlation between neuropathy severity and neurofilament light chain levels in Brazilian patients with hereditary transthyretin amyloidosis.Scientific reports · 2026Article
- Mispacking of the F87 sidechain drives aggregation-promoting conformational fluctuations in the subunit interfaces of the transthyretin tetramer.Protein science : a publication of the Protein Society · 2024Article
- Conformational Dynamics of an Amyloidogenic Intermediate of Transthyretin: Implications for Structural Remodeling and Amyloid Formation.Journal of molecular biology · 2024Article
- Role of conformational dynamics in pathogenic protein aggregation.Current opinion in chemical biology · 2023Review
- The Regulatory Mechanism of Transthyretin Irreversible Aggregation through Liquid-to-Solid Phase Transition.International journal of molecular sciences · 2023Article
- The role of α-sheet structure in amyloidogenesis: characterization and implications.Open biology · 2022Review
- Update on Disease-Specific Biomarkers in Transthyretin Cardiac Amyloidosis.Current heart failure reports · 2022Review
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Divergence Entropy-Based Evaluation of Hydrophobic Core in Aggressive and Resistant Forms of Transthyretin.Entropy (Basel, Switzerland) · 2021Article
- Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.International journal of molecular sciences · 2021Article
- Aggregation-Prone Structural Ensembles of Transthyretin Collected With Regression Analysis for NMR Chemical Shift.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
During amyloidogenesis, proteins undergo conformational changes that allow them to aggregate and assemble into insoluble, fibrillar structures. Soluble oligomers that form during this process typically contain 2-24 monomeric subunits and are cytotoxic. Before the formation of these soluble oligomers, monomeric species first adopt aggregation-competent conformations. Knowledge of the structures of these intermediate states is invaluable to the development of molecular strategies to arrest pathological amyloid aggregation. However, the highly dynamic and interconverting nature of amyloidogenic species limits biophysical characterization of their structures during amyloidogenesis. Here, we use molecular dynamics simulations to probe conformations sampled by monomeric transthyretin under amyloidogenic conditions. We show that certain β-strands in transthyretin tend to unfold and sample nonnative conformations and that the edge strands in one β-sheet (the DAGH sheet) are particularly susceptible to conformational changes in the monomeric state. We also find that changes in the tertiary structure of transthyretin can be associated with disruptions to the secondary structure. We evaluated the conformations produced by molecular dynamics by calculating how well molecular-dynamics-derived structures reproduced NMR-derived interatomic distances. Finally, we leverage our computational results to produce experimentally testable hypotheses that may aid experimental explorations of pathological conformations of transthyretin.
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Registered trials
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