Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation.
GTP Phosphohydrolases
/ chemistry
Membrane Fusion
/ genetics
Membrane Proteins
/ genetics
Mitochondria
/ metabolism
Mitochondrial Dynamics
/ genetics
Mitochondrial Membranes
/ metabolism
Mitochondrial Proteins
/ genetics
Mutant Proteins
/ metabolism
Plasmids
/ genetics
Protein Conformation, alpha-Helical
Protein Domains
Protein Processing, Post-Translational
/ genetics
Saccharomyces cerevisiae
/ enzymology
Saccharomyces cerevisiae Proteins
/ genetics
Ubiquitin
/ metabolism
Ubiquitination
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
28
06
2019
revised:
11
12
2019
accepted:
11
12
2019
entrez:
21
12
2019
pubmed:
21
12
2019
medline:
12
1
2021
Statut:
epublish
Résumé
Mitochondria are essential organelles whose function is upheld by their dynamic nature. This plasticity is mediated by large dynamin-related GTPases, called mitofusins in the case of fusion between two mitochondrial outer membranes. Fusion requires ubiquitylation, attached to K398 in the yeast mitofusin Fzo1, occurring in atypical and conserved forms. Here, modelling located ubiquitylation to α4 of the GTPase domain, a critical helix in Ras-mediated events. Structure-driven analysis revealed a dual role of K398. First, it is required for GTP-dependent dynamic changes of α4. Indeed, mutations designed to restore the conformational switch, in the absence of K398, rescued wild-type-like ubiquitylation on Fzo1 and allowed fusion. Second, K398 is needed for Fzo1 recognition by the pro-fusion factors Cdc48 and Ubp2. Finally, the atypical ubiquitylation pattern is stringently required bilaterally on both involved mitochondria. In contrast, exchange of the conserved pattern with conventional ubiquitin chains was not sufficient for fusion. In sum, α4 lysines from both small and large GTPases could generally have an electrostatic function for membrane interaction, followed by posttranslational modifications, thus driving membrane fusion events.
Identifiants
pubmed: 31857350
pii: 3/1/e201900476
doi: 10.26508/lsa.201900476
pmc: PMC6925385
pii:
doi:
Substances chimiques
Membrane Proteins
0
Mitochondrial Proteins
0
Mutant Proteins
0
Saccharomyces cerevisiae Proteins
0
Ubiquitin
0
FZO1 protein, S cerevisiae
EC 3.6.1.-
GTP Phosphohydrolases
EC 3.6.1.-
Banques de données
PDB
['5GOM', '5YEW', '5GOE', '2J69']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_U105192732
Pays : United Kingdom
Informations de copyright
© 2019 Schuster et al.
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