“…The overall mode of Vangl2 peptide engagement is conserved across all three PDZ domain complexes, with PDZ1, PDZ2 and PDZ3 engaging Vangl2 in a manner where the peptide is bound in an anti-parallel orientation compared to the second β-strand whilst being sandwiched by the α2 helix in the canonical binding pocket of the PDZ domains. A comparison of the PDZ1 and PDZ3 domain structures on their own with their Vangl2 complex counterparts revealed no significant movement of secondary structure elements upon Vangl2 binding, as previously observed in complexes of PDZ1 and PDZ3 with -PIX (Lim et al, 2017) and PDZ1 complexes with APC (How et al, 2019) and MCC (Caria et al, 2019 (Figure 2 B), key features of the PDZ1:Vangl2 complex are conserved, with V521 Vangl2 being located in a pocket formed by L872 PDZ2 , F874 PDZ2 , I876 PDZ2 , V932 PDZ2 and L935 PDZ2 , whilst the C-terminal carboxyl group forms hydrogen bonds with the main chain of L872 PDZ2 , G873 PDZ2 and F874 PDZ2 . Additional interactions are formed by S520 Vangl2 :S875 PDZ2 , T519 Vangl2 :H928 PDZ2 , as well as a salt bridge between E518 Vangl2 :S895 PDZ2 .…”