ArticleNature structural & molecular biology2025
The conformational landscape of human transthyretin revealed by cryo-EM.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Several multiple sequence alignment-perturbing methods enhance AlphaFold3 sampling of alternative protein states.Communications chemistry · 2026Article
- An N-terminal ATTR Fibril Segment Promotes Transthyretin Amyloid Nucleation and Polymorphism.bioRxiv : the preprint server for biology · 2026Article
- Investigating transthyretin variants H88R and I107V in amyloid priming: From destabilization to complete dissociation.The FEBS journal · 2026Article
- Structures of dye-bound transthyretin amyloid fibrils from abdominal fat biopsies.Nature communications · 2026Article
- DM: a simple solution to suppress air-water interface interactions in cryo-EM.bioRxiv : the preprint server for biology · 2026Article
- Phenomenological model of transthyretin stabilization.Scientific reports · 2026Article
- Mass spectrometry footprinting reveals how kinetic stabilizers counteract transthyretin dynamics altered by pathogenic mutations.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Amyloidogenic phenotypical variation affects post-transplant outcome of hereditary transthyretin amyloidosis: a retrospective study.eGastroenterology · 2026Article
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Dissecting Heterogeneous Populations of Protein-Complex Samples Using Direct Mass Technology.Analytical chemistry · 2025Article
- Effects of Hydration on Transthyretin Conformational Dynamics and Oligomerization.Biochemistry · 2025Article
- LARGE1 processively polymerizes length-controlled matriglycan on prodystroglycan.Nature communications · 2025Article
- Transthyretin Amyloidosis-One of the Causes of Heart Failure in Patients with Severe Clinical Course of COVID-19.International journal of molecular sciences · 2025Article
- Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV.Structure (London, England : 1993) · 2025Article
- Differentiating the solution structures and stability of transthyretin tetramer complexed with tolcapone and tafamidis using SEC-SWAXS and NMR.Journal of applied crystallography · 2025Article
- Advances in uncovering the mechanisms of macromolecular conformational entropy.Nature chemical biology · 2025Review
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Structure and Stabilities of Solution and Gas Phase Protein Complexes.Journal of the American Society for Mass Spectrometry · 2024Article
- The value of protein allostery in rational anticancer drug design: an update.Expert opinion on drug discovery · 2024Review
- High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.Journal of structural biology · 2024Article
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12 authors.
Funding
Abstract
Transthyretin (TTR) is a natively tetrameric thyroxine transporter in blood and cerebrospinal fluid whose misfolding and aggregation causes TTR amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndamax) as a stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency approved for the treatment of TTR amyloidosis. Here we used cryo-EM to investigate the conformational landscape of this 55 kDa tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states. These findings provide critical mechanistic insights into negatively cooperative ligand binding and the structural pathways responsible for TTR amyloidogenesis, underscoring the capacity of cryo-EM to identify pharmacological targets suppressed by the confines of the crystal lattice, opening uncharted territory in structure-based drug design.
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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.