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Arlek M. González-Jamett, Valentina Haro-Acuña, Fanny Momboisse, Pablo Caviedes, Jorge A. Bevilacqua and Ana M. Cárdenas Dynamin-2 in nervous system disorders Journal of Neurochemistry 128

Version of Record online: 23 OCT 2013 | DOI: 10.1111/jnc.12455

Thumbnail image of graphical abstract

Disease-linked dynamin-2 mutations are mainly located in the middle and pleckstrin homology (PH) domains. (a) Dynamin is a multimodular enzyme comprising five highly conserved structural domains: a N-terminal GTPase domain (G-domain) required for binding and hydrolysis of GTP, a middle domain, a PH domain that mediates lipid interaction, a GTPase effector domain (GED) that regulates GTPase activity, which together with the middle domain is involved in dynamin oligomerization. Finally, a C-terminal proline rich domain (PRD) is present, which is required for interaction with SH3-domain-containing proteins. (b) A ‘T-shape’ dimer appears to be the structural unit of dynamin oligomers (Chappie et al. 2011). In this configuration, the PH domains (yellow) of neighboring monomers act as the ‘legs’ that insert dynamin into lipid membranes. Each ‘stalk’ region formed by the middle (green) and GED (red) domains interacts with the other in a crossed fashion, orienting the respective G-domains (blue) in opposite directions. Most of the mutations identified in CNM-patients (at the left) localize at the middle and C-terminal α-helix PH domains, both of which are implicated in dynamin oligomerization. Most of the CMT-linked mutations (at the right) clustering at the N-terminal region of the PH domain are involved in the insertion of dynamin into lipid membranes. Color code for structural domains and letters indicating the mutations are the same as those shown in A. In this diagram, PRD is omitted.

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