2025 — HERV-K Env cryo-EM structures (pre- and post-fusion)
One-paragraph summary
Experimental cryo-EM determination of HERV-K envelope protein in both pre-fusion and post-fusion conformations. Used iterative AlphaFold + DeepCoil predictions to design helix-breaking mutations stabilizing the pre-fusion state for structural determination. Provides experimental gold-standard structural ground truth for HERV-K Env, enabling validation of AlphaFold predictions against measured structure. Methodology — combining cryo-EM with AlphaFold-driven mutation design — is directly applicable to other HERV envelope proteins. Establishes that HERV-K Env retains canonical retroviral envelope architecture (HR1/HR2 heptad repeat helices, fusion peptide).
Claims as triples
- HERV_K — present_in → fm_central_only [contextual; confidence: emerging]
Methods note
Cryo-EM at moderate-to-high resolution. AlphaFold-driven mutagenesis to capture pre-fusion intermediate. Posttranslational processing and oligomerization screened for each mutant.
Limitations
- Single-protein structural study; doesn't test FM-relevance directly.
- Pre-fusion stabilization required engineered mutations — wild-type HERV-K Env may behave differently in patient cells.
Triangulation notes
- Validates Q40 pipeline methodology — AlphaFold structural prediction + mutational design has been successfully applied to HERV-K family. The pipeline's structural predictions for HERV-K Env can be cross-validated against this experimental data.
- Reference structure for the pipeline's Step 6 (AlphaFold 3 docking against cGAS/STING/TLR4) — HERV-K Env vs cGAS/STING binding can be predicted with confidence in the structural input.