(A) Combined surface and ribbon-stick model showing the structural basis for the formation of the KIBRA WW tandem supramodule. The detailed interactions between the inter-domain linker and C-terminal α-helix (αC) are shown in an expanded insert at right. The residues chosen for mutational analysis in Panel B are boxed. (B) ITC-based measurements comparing the binding affinities of the KIBRA WW tandem and its various mutants to PTPN14 PY12. (C) Amino acid sequence alignment of the WW tandems from KIBRA, MAGI1, MAGI2, MAGI3, YAP, SAV1, WWOX and ITCH-WW12/WW34, showing that the WW tandems of KIBRA, MAGI2, and MGAI3 are more similar to each other. (D) ITC-derived affinities of various WW tandems binding to PTPN14 PY12 and LATS1 PY23. (E) Combined ribbon and stick diagram showing the structure and detailed interaction of the MAGI2 WW tandem in complex with Dendrin PY23. The detailed interactions between the inter-domain linker and C-terminal α-helix are shown in an expanded box below the structure. (F) Ribbon and stick model showing the superimposition of two versions of the structures of YAP WW tandem in complex with Dendrin PY23. The structure colored in brown was obtained by fusing Dendrin-PY23 to the N-terminus of the YAP WW tandem, and the one colored in cyan was obtained by fusing Dendrin-PY23 to the C-terminus of the YAP WW tandem. The structures are superimposed by overlaying the WW1, showing different orientations of WW2 between the two structures. The dotted lines denote the linking sequence between WW1 and WW2, which could not be traced in the two crystal structures.