ArticleNature communications2025
Energetic profiling reveals thermodynamic principles underlying amyloid fibril maturation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Assembling peptides for treating Alzheimer's disease: a supramolecular perspective.RSC advances · 2026Review
- An N-terminal ATTR Fibril Segment Promotes Transthyretin Amyloid Nucleation and Polymorphism.bioRxiv : the preprint server for biology · 2026Article
- TAF15 amyloids propagate via defined motifs in a prion-like fashion.Nature communications · 2026Article
- The amyloid packing difference: A pairwise comparison metric for amyloid structures.Structure (London, England : 1993) · 2026Article
- A functional amyloid scaffold shapes insect egg coats.bioRxiv : the preprint server for biology · 2026Article
- Amyloid fibril polymorphism: Structural mechanisms of assembly and the links to disease.Current opinion in structural biology · 2026Review
- Reverse-engineering amyloid strains with generative protein design.bioRxiv : the preprint server for biology · 2026Article
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Authors and funding
4 authors.
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Abstract
Amyloid fibrils adopt diverse structural polymorphs linked to disease-specific phenotypes, but the thermodynamic principles guiding their formation and maturation remain unclear. Here, we apply energetic profiling to structural time series from cryo-EM datasets of IAPP, tau, and α-synuclein to decode the principles governing fibril maturation and polymorphic divergence. By mapping residue-level free energy contributions across experimentally resolved assembly pathways, we reconstruct their maturation trajectories and find that amyloid assembly is anchored by aggregation-prone regions that serve as sequence-encoded stabilizing motifs. As assembly progresses, these motifs are reorganized and expanded, while additional regions introduce structural frustration that enables conformational flexibility. Environmental cofactors such as metal ions or polyanions are observed in association with regions of structural remodeling, where they may act to compensate for otherwise energetically strained conformations. This framework offers mechanistic insight into how distinct polymorphs arise from a common sequence and mature through both intrinsic and extrinsic thermodynamic influences.
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