SUMO-2 activity is inhibited by non-covalent interactions with the Aβ peptide: an exploration of potential pathogenic mechanisms in Alzheimer's disease
Bibliographic record
Abstract
SUMOylation is a post-translational modification involving the addition of SUMO isoforms to target proteins and plays a role in various biological processes, including neurodegenerative diseases and ocular pathologies. This study investigates the interaction between SUMO-2 and amyloid (Aβ) peptides, key contributors to Alzheimer's disease, using techniques like cross-linking mass spectrometry, surface plasmon resonance and biolayer interferometry. Data are available via ProteomeXchange with identifier PXD066055. The results show that Aβ1-40 and Aβ1-42 bind more strongly to SUMO-2 than to ubiquitin, with binding driven by specific hydrogen bonds and hydrophobic interactions. SUMO-2 was found to inhibit the conversion of Aβ into β-sheet structures and impede Aβ aggregation. Notably, Aβ competes with SUMO-2 canonical substrates for binding, completely hindering SUMOylation reactions in vitro. Identifying SUMO-2/Aβ1-42 adducts in cellular extracts and live cells further highlights the biological significance of these interactions. Overall, the findings indicate that Aβ peptides impair SUMO-2 function, pointing to the necessity for more research on the implications of SUMOylation in Alzheimer's disease.
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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".