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. Author manuscript; available in PMC: 2009 Jul 16.
Published in final edited form as: Nat Rev Neurosci. 2008 Jul;9(7):505–518. doi: 10.1038/nrn2417

Figure 4. Mutations in Mfn2 and OPA1 present in human patients.

Figure 4

(a) Domain model of Mfn2 (Swissprot: O95140) showing location of the GTPase domain and the putative Neck, Trunk, and Paddle domains. Red arrows indicate locations of missense mutations found in CMT-2A patients (OMIM database: 608507). (b) Homology model of human Mfn2 residues 24-757 shown in ribbon presentation, indicating the GTPase, Neck, Tip, Paddle, and Trunk region based on the crystal structure of bacterial dynamin-like protein (PDB-ID 2j68 (2), FFAS (1) score - 67.0, sequence identity 11%). Red spheres indicate mutations found in CMT2A. (c) Domain model of OPA1 with locations of missense mutations found in ADOA patients (top) (OMIM database: 165500) indicated by red arrows and ‘OPA1-plus’ disorders (bottom) indicated by black arrows. (d) Homology model of the OPA1 GTPase domain (residues 244-575) based on the dynamin GTPase domain (1jw1.pdb) shown in ribbon representation with a GDP molecule bound in the putative active site shown in ball and stick. Red spheres indicate residues mutated in ADOA patients (eOPA1)5. A close up view of the active site in OPA-1 shows native (gray) and mutant (yellow) side-chains for comparison. The model clearly shows that several mutations directly interfere with GTP binding and most probably impair the catalytic function. Models were prepared with PyMOL (DeLano Scientific).