Skip to Main content Skip to Navigation
Journal articles

A membrane-inserted structural model of the yeast mitofusin Fzo1

Abstract : Mitofusins are large transmembrane GTPases of the dynamin-related protein family, and are required for the tethering and fusion of mitochondrial outer membranes. Their full-length structures remain unknown, which is a limiting factor in the study of outer membrane fusion. We investigated the structure and dynamics of the yeast mitofusin Fzo1 through a hybrid computational and experimental approach, combining molecular modelling and all-atom molecular dynamics simulations in a lipid bilayer with site-directed mutagenesis and in vivo functional assays. The predicted architecture of Fzo1 improves upon the current domain annotation, with a precise description of the helical spans linked by flexible hinges, which are likely of functional significance. In vivo site-directed mutagenesis validates salient aspects of this model, notably, the long-distance contacts and residues participating in hinges. GDP is predicted to interact with Fzo1 through the G1 and G4 motifs of the GTPase domain. The model reveals structural determinants critical for protein function, including regions that may be involved in GTPase domain-dependent rearrangements.
Complete list of metadata

Cited literature [81 references]  Display  Hide  Download
Contributor : Gestionnaire Hal-Upmc Connect in order to contact the contributor
Submitted on : Tuesday, September 5, 2017 - 2:32:55 PM
Last modification on : Friday, December 3, 2021 - 3:15:02 AM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License



Dario de Vecchis, Laetitia Cavellini, Marc Baaden, Jérôme Hénin, Mickaël M. Cohen, et al.. A membrane-inserted structural model of the yeast mitofusin Fzo1. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.10217. ⟨10.1038/s41598-017-10687-2⟩. ⟨hal-01581980⟩



Les métriques sont temporairement indisponibles