“…Lastly, the conserved His in each domain found on a2, PDZ1 H793, PDZ2 H928, and PDZ3 H1071, shared a hydrogen bond with Thr351 Tax1 , and mutation to Ala ablates Tax1 binding to SCRIB PDZ domains as seen in our ITC analysis (Table 1, Figs 1B and 3). This particular conserved His residue is also involved in interactions with other cellular and viral interactors of Scribble as observed in crystal structures of SCRIB PDZ1:b-PIX, PDZ3:b-PIX, PDZ1:MCC, PDZ1:APC, PDZ1:Vangl2, PDZ2: Vangl2, PDZ3:Vangl2, PDZ1: NS1, and PDZ3:NS1 [20,37,[43][44][45], thus making this residue vital for SCRIB:ligand interactions.…”