Fig. 1

The PINK1 p.I368N mutation is positioned in the kinase domain and alters the ATP-binding site. a Domain structure of human PINK1 protein. Individual domains are color-coded and labeled: mitochondrial targeting sequence (MTS); transmembrane domain (TM); N-terminal, regulatory domain (NT); N-lobe and C-lobe of the kinase domain; C-terminal domain (CTD). Residues surrounding Ile368 were aligned with corresponding sequences of PINK1 orthologs from different species. Horizontal bar denotes the catalytic loop in kinase subdomain VIb. b Root mean square fluctuations (RMSF) of the entire PINK1 structures. Dotted lines separate individual domains of PINK1 that include MTS, TM, NT, kinase domain and CTD. An arrow highlights the position of the p.I368N mutation. c Superposition overlay of the kinase domains before and after 50 ns of MDS. Structures are shown in cartoon ribbons with PINK1 WT in gray and p.I368N mutant in color according to the domain structure in (a). Residues Ile368 and Asn368 are shown in licorice rendering using gray or standard atom coloring, respectively. The Mg²⁺ ions are gray colored Van der Waals (VdW) spheres for both and the ATP-analogs in the active sites are shown in gray for WT and Goodsell coloring for p.I368N. d Root mean square deviation (RMSD) of the kinase domain of PINK1 WT and p.I368N mutant, shows only minor structural differences. e Zoom into the ATP-binding sites of PINK1 WT and p.I368N mutant in superposition overlay before and after 50 ns of MDS as described for (c). f RMSD of the ATP-binding pocket in the kinase domains of WT and mutant PINK1. Pocket residues include positions: 161,163, 217, 218, 219, 237, 240, 275, 316, 318, 319, 320, 321, 322, 325, 326, 327, 362, 363, 365, 366, 367, 368, 369, 383, 384, 385, 386, and 387. g The surface of the ATP-binding pocket of WT and p.I368N mutant PINK1 is shown for comparison in standard atom coloring. The Mg²⁺ ion (VdW sphere) and the ATP-analog (sticks colored by atom type) in the active site are given. h Radius of gyration measurements on the ATP-binding pocket from WT and mutant PINK1 provides the extent to which an object is extended from its center of mass