A membrane-inserted structural model of the yeast mitofusin Fzo1

TitleA membrane-inserted structural model of the yeast mitofusin Fzo1
Publication TypeJournal Article
Year of Publication2017
AuthorsDe Vecchis D, Cavellini L, Baaden M, Hénin J, Cohen MM, Taly A
JournalSci Rep
Volume7
Issue1
Pagination10217
Date Published2017 Aug 31
Type of ArticleResearch Article
ISSN2045-2322
Other NumbersANR-11-LABX-0011
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.

DOI10.1038/s41598-017-10687-2
Alternate JournalSci Rep
Citation Key2017|2021
Refereed DesignationRefereed
PubMed ID28860650
PubMed Central IDPMC5578988