Fig. 1

Phosphorylated INCENP binds the activation loop of Aurora kinase B/C. a Structure of activated AURKC bound to the phosphorylated INCENP “IN-box”. b, c Views from two angles showing how the phosphorylated INCENP makes extensive hydrogen-bonding interactions with the activation loop and αC-helix of AURKC, and contributes significantly to arranging the active conformation and substrate binding region of the kinase. d Sequence alignment of the αC and activation loop regions of AURKB or AURKC from diverse organisms. Residues involved in binding INCENP are marked with triangles below the alignment. For a full sequence alignment and sequence accession numbers see Supplementary Fig. 4. The sequence alignment was created using ClustalO⁴⁶ and Aline⁴⁷. e In the fully active AURKC:INCENP structure INCENP makes contact with the Aurora kinase N-lobe and C-lobe, and the activation loop. f, g Views from two angles showing how INCENP binds on two sides of AURKC αC including an aromatic stacking interaction between INCENP W897 and AURKC H97 and H190, as well as the hydrogen-bonding network around INCENP pS893 and pS894. These binding interactions link AURKC αC and activation loop into a stable conformation, and the INCENP phosphorylations help to form the substrate binding groove, thus activating AURKC to different substrates