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TitleStructure of the endosomal CORVET tethering complex.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 5227, Year 2024
Publish dateJun 19, 2024
AuthorsDmitry Shvarev / Caroline König / Nicole Susan / Lars Langemeyer / Stefan Walter / Angela Perz / Florian Fröhlich / Christian Ungermann / Arne Moeller /
PubMed AbstractCells 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 ...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.
External linksNat Commun / PubMed:38898033 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 8.5 Å
Structure data

14964

7zu0

EMDB-14964: HOPS tethering complex from yeast, composite map
PDB-7zu0: HOPS tethering complex from yeast
Method: EM (single particle) / Resolution: 4.4 Å

18701

8qx8

EMDB-18701, PDB-8qx8:
Endosomal membrane tethering complex CORVET
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-18702: Endosomal membrane tethering complex CORVET, Vps8-Vps11 local refinement map
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-18703: Endosomal membrane tethering complex CORVET, Vps8 beta propeller local refinement map
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-18704: Endosomal membrane tethering complex CORVET, SNARE binding module local refinement map
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-18705: Endosomal membrane tethering complex CORVET, core local refinement map
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-18706: Endosomal membrane tethering complex CORVET, Vps18 beta propeller local refinement map
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-18707: Endosomal membrane tethering complex CORVET, consensus map
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-18708: Endosomal membrane tethering complex CORVET, Vps11deltaN mutant
Method: EM (single particle) / Resolution: 8.5 Å

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsCYTOSOLIC PROTEIN / HOPS / tethering complex / lysosome / membrane fusion / Rab GTPase / cryo-EM / ENDOCYTOSIS / CORVET / endosome / tethering

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