Figure 7. Model for the co-evolution of AcrVA4 susceptibility.
The ancestral Cas12a likely possessed a helical bundle, hindering any exploitation of the processing nuclease and bridge-helix (bottom left). While AsCas12a maintained the ancestral helical bundle and resistance to Acr activity at that site (top right), LbCas12a and related orthologs lost the helical bundle, providing a co-evolutionary opportunity for AcrVA4 allosteric inhibition.
