نبذة مختصرة : Most harmful rhabdoviruses cause disease that is invariably lethal to humans, animals and plants. Throughout viral infection, protein refolding is a complex process critical to both receptor recognition and membrane-interacting fusion domains mediated by transmembrane rhabdoviral glycoprotein (Gp). However, little is known about the early stages of context-sensitive structural transitions of the rhabdoviral Gp. We hypothesized that these involve local interactions between residues situated in intrinsically disordered regions (IDRs) of both the β-sheet rich lateral domain and the fusion domain. This study investigates the host-specific biophysical IDRs-determinants encoded in the primary amino acid sequence of rhabdoviral glycoproteins, which are predicted to modulate early conformational events. This can be related to host-specific biophysical features of the local backbone and secondary structure propensities close to or in IDRs of Gps. While showing striking differences between IDRs of N- and C-termini, our results give direct insights into the biophysical folding signals located in these regions and are in congruence with independent experimental observations. Furthermore, on a quantitative scale, the biophysical features of these residues tend to become those that interact the most in the folded structure and are often residues that display evolutionary covariation, reflecting a general tendency toward conserved host-specificity. In conclusion, the accurate connection of biophysical structural features with both IDRs conformational propensities and context-sensitive folding data suggests their statistically significant role in local transition with lasting effects on subsequent conformational states during virus-host interactions and disease-related pathogenicity outcomes.
Prediction and validation of biological properties of viruses using -omic data through machine learning.
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