Structure of the endosomal CORVET tethering complex.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
09
11
2023
accepted:
24
05
2024
medline:
20
6
2024
pubmed:
20
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
Cells depend on their endolysosomal system for nutrient uptake and downregulation of plasma membrane proteins. These processes rely on endosomal maturation, which requires multiple membrane fusion steps. Early endosome fusion is promoted by the Rab5 GTPase and its effector, the hexameric CORVET tethering complex, which is homologous to the lysosomal HOPS. How these related complexes recognize their specific target membranes remains entirely elusive. Here, we solve the structure of CORVET by cryo-electron microscopy and revealed its minimal requirements for membrane tethering. As expected, the core of CORVET and HOPS resembles each other. However, the function-defining subunits show marked structural differences. Notably, we discover that unlike HOPS, CORVET depends not only on Rab5 but also on phosphatidylinositol-3-phosphate (PI3P) and membrane lipid packing defects for tethering, implying that an organelle-specific membrane code enables fusion. Our data suggest that both shape and membrane interactions of CORVET and HOPS are conserved in metazoans, thus providing a paradigm how tethering complexes function.
Identifiants
pubmed: 38898033
doi: 10.1038/s41467-024-49137-9
pii: 10.1038/s41467-024-49137-9
doi:
Substances chimiques
Phosphatidylinositol Phosphates
0
phosphatidylinositol 3-phosphate
0
rab5 GTP-Binding Proteins
EC 3.6.5.2
Vesicular Transport Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5227Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : MO2752/3-6
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 944
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 1557
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : INST190/196-1 FUGG
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 944
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 1557
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 944
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 1557
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01ED2010
Informations de copyright
© 2024. The Author(s).
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