Structural Properties and Dynamic Behavior of Nonfibrillar Oligomers Formed by PrP(106−126)
Bibliographic record
Abstract
The formation of nonfibrillar oligomers has been proposed as a common element of the aggregation pathway of proteins and peptides associated with neurodegenerative diseases such as Alzheimer's and Creutzfeldt-Jakob disease. While fibrillar structures have long been considered indicators of diseases linked with the accumulation of amyloid plaques, it has more recently been proposed that amyloid oligomers are in fact the cytotoxic form. Here we describe the local structure and dynamics of stable oligomers formed by a peptide comprising residues 106-126 of the human prion protein (PrP). Structural constraints from solid-state NMR reveal quaternary packing interactions within the hydrophobic core, similar to those previously reported for amyloid fibrils formed by this peptide, and consistent with structural studies of oligomers formed by the Alzheimer's beta-amyloid peptide. However, a hydration-dependent increase in disorder is observed for nonfibrillar oligomers of PrP(106-126). In solution NMR spectra we observe narrow (1)H and (13)C resonances corresponding to a monomer in exchange with the approximately 30 nm diameter nonfibrillar oligomers, giving additional information on the molecular structure of these species. Taken together, our data support a model in which the local structure of the oligomers contains the basic elements of amyloid fibrils, but with long-range disorder and local mobility that distinguishes these assemblies from the fibrillar form of PrP(106-126). These characteristics may provide a basis for the differing biological activities of amyloid fibrils and oligomers.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".