Figure 6

Structural predictions of the effects of the MTM1 p.(Q384P) mutation. Jmol visualizations of predicted structural models of full-length canine myotubularin generated by Phyre2 (A) show the PH-GRAM domain (yellow) oriented at the top and the phosphatase domain (light blue) below. The SET and coiled coil domains are shown in blue and purple, respectively (as in Figure 5B). The P-loop is colored green and the position of Q384 is shown in red. The region encompassing β-sheet 14, the P-loop, and α-10 (residues 370-394), is shown in isolation for the wild type protein (B), and for the p.(Q384P) mutation (C). Note loss of alpha helical structure at arginine 381 (indicated). Repeating the Phyre2 structural predictions for just the 30 residue peptide including positions 369-398 and modeling space-filling atoms for positions 381 and 384 illustrates predicted steric interference between R381 and mutated P394 (E), but not wild type Q384 (D) (arrowheads).