ArticleAnnals of clinical and translational neurology2019
Biophysical characterization and modulation of Transthyretin Ala97Ser.
Article in Annals of clinical and translational neurology, 2019. 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.
- Structures of dye-bound transthyretin amyloid fibrils from abdominal fat biopsies.Nature communications · 2026Article
- Differentiating the solution structures and stability of transthyretin tetramer complexed with tolcapone and tafamidis using SEC-SWAXS and NMR.Journal of applied crystallography · 2025Article
- Diflunisal versus tafamidis on neuropathy and cardiomyopathy in hereditary transthyretin amyloidosis.Annals of clinical and translational neurology · 2024Article
- A Comprehensive Review on Chemistry and Biology of Tafamidis in Transthyretin Amyloidosis.Mini reviews in medicinal chemistry · 2024Review
- Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis.Therapeutic advances in chronic disease · 2024Article
- Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS.PLoS biology · 2024Article
- The genetic and clinical spectrum in a cohort of 39 families with complex inherited peripheral neuropathies.Journal of neurology · 2023Article
- A molecular basis for tetramer destabilization and aggregation of transthyretin Ala97Ser.Protein science : a publication of the Protein Society · 2023Article
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.International journal of molecular sciences · 2021Article
- Cellular secretion and cytotoxicity of transthyretin mutant proteins underlie late-onset amyloidosis and neurodegeneration.Cellular and molecular life sciences : CMLS · 2020Article
- Analysis of gene variants in the GASH/Sal model of epilepsy.PloS one · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
objectiveAla97Ser (A97S) is the major transthyretin (TTR) mutation in Taiwanese patients of familial amyloid polyneuropathy (FAP), characterized by a late-onset but rapidly deteriorated neuropathy. Tafamidis can restore the stability of some mutant TTR tetramers and slow down the progression of TTR-FAP. However, there is little understanding of the biophysical features of A97S-TTR mutant and the pharmacological modulation effect of tafamidis on it. This study aims to delineate the biophysical characteristics of A97S-TTR and the pharmacological modulation effect of tafamidis on this mutant.
methodThe stability of TTR tetramers was assessed by urea denaturation and differential scanning calorimetry. Isothermal titration calorimetry (ITC) was used to measure the binding constant of tafamidis to TTR. Nuclear magnetic resonance spectroscopy (NMR) titration experiment was used to map out the tafamidis binding site.
resultsChemical and thermal denaturation confirmed the destabilization effect of A97S. Consistent with other the amyloidogenic mutant, A97S-TTR has slightly lower conformational stability. NMR revealed the binding site of A97S-TTR with tafamidis is at the thyroxine binding pocket. The ITC experiments documented the high affinity of the binding which can effectively stabilize the A97S-TTR tetramer.
interpretationThis study confirmed the structural modulation effect of tafamidis on A97S-TTR and implied the potential therapeutic benefit of tafamidis for A97S TTR-FAP. This approach can be applied to investigate the modulation effect of tafamidis on other rare TTR variants and help to make individualized choices of available treatments for FAP patients.
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