Galectin-3 as Damage-Sensor Scaffold for Multimeric Cross-Seeding at Compromised Endo/Lysosomal Membranes
🧪 Overview
Galectin-3's carbohydrate recognition domain binds exposed glycans on ruptured endolysosomal membranes while its intrinsically disordered N-terminus provides a phase-separated condensation surface that recruits aggregation-prone proteins (Aβ42, α-synuclein, TDP-43) into localized high-concentration environments favoring cross-nucleation.
🧬 Mechanism
Curated pathway from expert analysis
flowchart TD
A["Endolysosomal Membrane Rupture<br/>Amyloid or Oxidative Stress"]
B["Luminal Glycan Exposure<br/>beta-galactose on Damaged Membranes"]
C["LGALS3 Galectin-3 CRD Domain<br/>Carbohydrate Recognition Domain Binds"]
D["LGALS3 N-Terminal IDR<br/>Intrinsically Disordered Phase-Sep Region"]
E["Phase-Separated Condensate<br/>Galectin-3 Scaffold at Rupture Site"]
F["Aggregation-Prone Protein Concentration<br/>Cross-Seeding Opportunity"]
G["Tau SNCA TDP43 FUS Recruitment<br/>Multi-Protein Cross-Seeding"]
H["Multimeric Amyloid Propagation<br/>Endolysosomal Rupture Amplified"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style E fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — LGALS3
No curated PDB or AlphaFold mapping for LGALS3 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for LGALS3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |