Structural and biochemical characterization of the interaction between LGN and Frmpd1

The tetratricopeptide repeat (TPR) motif-containing protein LGN binds multiple targets and regulates their subcellular localizations and functions during both asymmetric and symmetric cell divisions. Here, we characterized the interaction between LGN TPR motifs and FERM and PDZ domain containing 1 (Frmpd1), and reported the crystal structure of the complex at 2.4-Å resolution. A highly conserved fragment at the center of Frmpd1 of ~ 20 residues was found to be necessary and sufficient to bind to LGN-TPR. This Frmpd1 fragment forms an extended structure and runs along the concave channel of the TPR superhelix in an antiparallel manner in the complex. Structural comparisons and biochemical studies of LGN/Frmpd1, and other known LGN/target interactions demonstrate that the LGN TPR motifs are versatile and capable of recognizing multiple targets via diverse binding modes. Nevertheless, a conserved “E/QxEx4-5E/D/Qx1-2K/R”-motif in LGN/Pins TPR binding proteins has been identified. ⺠LGN binds diverse targets through its TPR motifs. ⺠The crystal structure of the LGN TPR/Frmpd1 complex was solved. ⺠A consensus LGN TPR recognition sequence of “E/QxEx4-5E/D/Qx1-2K/R” was summarized. ⺠The LGN TPR motifs serve as a versatile platform for protein-protein interaction.