Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2‐step entry mechanism
Bibliographic record
Abstract
Entry of enveloped viruses into host cells is mediated by their surface envelope glycoproteins (Env). On the surface of the virus, Env is in a metastable, prefusion state, primed to catalyze the fusion of the viral and host membranes. An external trigger is needed to promote the drastic conformational changes necessary for the fusion subunit to fold into the low-energy, 6-helix bundle. These triggers typically facilitate pH-independent entry at the plasma membrane or pH-dependent entry in a low-pH endosomal compartment. The α-retrovirus avian sarcoma leukosis virus (ASLV) has a rare, 2-step entry mechanism with both pH-dependent and pH-independent features. Here, we present the 2.0-Å-resolution crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural and biophysical studies indicated that unlike other pH-dependent or pH-independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two histidine residues (His490 and His492) in the chain reversal region confer stability at low pH. A structural comparison of class I viral fusion proteins suggests that the presence of a positive charge, either a histidine or arginine amino acid, stabilizes a helical dipole moment and is a signature of fusion proteins active at low pH. The structure now reveals key residues and features that explain its 2-step mechanism, and we discuss the implications of the ASLV TM structure in the context of general mechanisms required for membrane fusion.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.003 | 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 teacher head, 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".