ArticleProceedings of the National Academy of Sciences of the United States of America2012
Conserved features of intermediates in amyloid assembly determine their benign or toxic states.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 132 citations in OpenAlex.
- Single-Molecule Techniques for Probing the Conformation, Dynamics and Interactions of Intrinsically Disordered Proteins.Biophysics reviews · 2025Article
- Deciphering Amyloid Fibril Formation through Protein Concentration by Optical Trapping.JACS Au · 2025Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Multidimensional Super-Resolution Microscopy Unveils Nanoscale Surface Aggregates in the Aging of FUS Condensates.Journal of the American Chemical Society · 2023Article
- Characterization of Pairs of Toxic and Nontoxic Misfolded Protein Oligomers Elucidates the Structural Determinants of Oligomer Toxicity in Protein Misfolding Diseases.Accounts of chemical research · 2023Article
- Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures.Viruses · 2022Review
- Quantitative Measurement of the Affinity of Toxic and Nontoxic Misfolded Protein Oligomers for Lipid Bilayers and of its Modulation by Lipid Composition and Trodusquemine.ACS chemical neuroscience · 2021Article
- Identification of transmissible proteotoxic oligomer-like fibrils that expand conformational diversity of amyloid assemblies.Communications biology · 2021Article
- Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity.International journal of molecular sciences · 2021Review
- Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold.BMC biology · 2021Article
- Single Molecule Characterization of Amyloid Oligomers.Molecules (Basel, Switzerland) · 2021Review
- Dynamics of oligomer and amyloid fibril formation by yeast prion Sup35 observed by high-speed atomic force microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Ratiometric Single-Molecule FRET Measurements to Probe Conformational Subpopulations of Intrinsically Disordered Proteins.Current protocols in chemical biology · 2020Article
- Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli.Nature communications · 2020Article
- Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms.Current opinion in neurobiology · 2019Review
- Self-triggered click reaction in an Alzheimer's disease model:Chemical science · 2019Article
- Single-molecule fluorescence studies of intrinsically disordered proteins and liquid phase separation.Biochimica et biophysica acta. Proteins and proteomics · 2019Review
- Atomic resolution map of the soluble amyloid beta assembly toxic surfaces.Chemical science · 2019Article
- Transition of Metastable Cross-α Crystals into Cross-β Fibrils by β-Turn Flipping.Journal of the American Chemical Society · 2019Article
- A Bifunctional Anti-Amyloid Blocks Oxidative Stress and the Accumulation of Intraneuronal Amyloid-Beta.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembly of a normal, functional amyloid, the prion-determining region of yeast Sup35 (NM). During assembly, NM formed a variety of oligomers with different sizes and conformation-specific antibody reactivities. Earlier oligomers were less compact and reacted with the conformational antibody A11. More mature oligomers were more compact and reacted with conformational antibody OC. We found we could arrest NM in either of these two distinct oligomeric states with small molecules or crosslinking. The A11-reactive oligomers were more hydrophobic (as measured by Nile Red binding) and were highly toxic to neuronal cells, while OC-reactive oligomers were less hydrophobic and were not toxic. The A11 and OC antibodies were originally raised against oligomers of Aβ, an amyloidogenic peptide implicated in Alzheimer's disease (AD) that is completely unrelated to NM in sequence. Thus, this natural yeast prion samples two conformational states similar to those sampled by Aβ, and when assembly stalls at one of these two states, but not the other, it becomes extremely toxic. Our results have implications for selective pressures operating on the evolution of amyloid folds across a billion years of evolution. Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike.
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