t OLGs have a tendency to encode proteins with higher intrinsic structural disorder
Or they tend to be proteins where the fold is relatively resistant to changes in amino acid sequence?
9 Matching Annotations
- Jun 2025
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Specifically, we investigated the hypothesis that the Rs3367-CoV spike, like SHC014-CoV but not WIV1-CoV, predominantly assumes a closed “all RBDs down” conformation that cannot bind its cellular receptor, ACE2, and that this property is modulated by Y623H.
Its an interesting question how this ultimately works in the wild. I guess at low pH in bat enteric tract theres enough up, even with the wild type sequence?
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Our results suggest alternative spillover scenarios in which spike-opening substitutions that promote virus-receptor binding and entry could precede, or even initially replace, substitutions that enhance spike cleavage in the zoonotic host.
Really significant to identify potential alternative spillover adaptations. If a single amino acid change can achieve something similar to an S1/S2 furin cleavage site, suggests spillover barrier may be lower than we thought. otoh, if these are strongly selected against in the wild, then maybe still requires an unusual circumstance.
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The designed VIProDesign Betacoronavirus panel consists of 24 strains from five Betacoronavirus subgroups: Nobecovirus, Sarbecovirus, Hibecovirus, Merbecovirus, and Embecovirus. Not all Betacoronavirus subgroups infect humans, although some animal-borne infections are known to present risk to humans (Chen, et al., 2025; Frutos, et al., 2021). When the DBSCAN outlier detection algorithm was applied to the Betacoronavirus dataset (Supplementary Figure 1a), the Nobecovirus and Hibecovirus subgroups were eliminated. This suggests that outlier detection is not suitable in this case, due to the limited number of strains (n = 200) in the Betacoronavirus set.
Even ones that dont infect humans could represent meaningful diversity that could be valuable for this work.
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The VIProDesign_Betacoronavirus_24 panel comprised 24 strains (Fig. 2a), including five Sarbecovirus, four Nobecovirus, two Hibecovirus, five Merbecovirus, and eight Embecovirus strains.
Meaning - i'm not sure the designed panel necessarily represents as much diversity as it could.
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The VIProDesign_Betacoronavirus_24 panel comprised 24 strains (Fig. 2a), including five Sarbecovirus, four Nobecovirus, two Hibecovirus, five Merbecovirus, and eight Embecovirus strains.
I think this left a lot of diversity on the table - I'm not sure why. At the same time, these differ compared to the other viral groups by using different (tho also in some cases unknown receptors). I think a more thorough search could produce much more diversity for this dataset.
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Next, sequence redundancy is removed by applying CD-HIT (Li and Godzik, 2006) with a 99% cutoff.
It would be interested to see how downstream results vary depending on the sensitivity cutoff. It seems like 99% isnt going to remove that much redundancy, and possibly a lower cutoff would still capture the diversity while streamlining experimental efficiency
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- Mar 2025
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While the nature or function of these filaments remain unknown, these observations suggest that they may help mediate physical attachment and symbiotic interactions with partner organisms. Notably, prokaryotic filament structures—flagella, pili, and archaella—have been repeatedly
Could there be any relationship to flagella of unicellular eukaryotes?
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Phylogenetic analyses suggest FECA may have also had low aerotolerance but did not respire oxygen, like HC1 (Fig. 5g). This strongly indicates that the prokaryote-eukaryote transition was steep in both cell structure and physiology—from anaerobic to aerobic and from simple to complex internal cell structure.
It seems possible some degree of oxygen respiration could have been acquired on the branch leading to FECA. I think much is still unknown about this.
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