3.3.3 Iota toxin-component has increased connectivity when bound to actin protein.
The Iota toxin component Ia is an ADP ribosylating toxin (ADPRT). The C-terminal domain that houses the active site of this protein complexed to NAD is essential for its function. It is known that the active site loop along with residues Tyr60-Tyr62 of the toxin binds to actin protein and inhibits its activity. Actin specific ADPRTs perform ADP ribosylation of G-actin at Arg117, leading to disorganisation of the cytoskeleton and cell death.
In our analysis, significant dissimilarity is observed between the actin bound form of the protein (PDB ID 3BUZ shown in Supplementary Figure 3C) and the unbound toxin. The actin bound protein has few more new interactions at the binding site and a net overall gain in connectivity. New edges are found to be gained at the functional sites Arg352, Glu378, Glu380 of the protein. A net gain in number of edges and hubs is observed, which shows a more compact structure especially around the binding site (Figure 2C).