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TitleArchitecture and mechanism of metazoan retromer:SNX3 tubular coat assembly.
Journal, issue, pagesSci Adv, Vol. 7, Issue 13, Year 2021
Publish dateMar 24, 2021
AuthorsNatalya Leneva / Oleksiy Kovtun / Dustin R Morado / John A G Briggs / David J Owen /
PubMed AbstractRetromer is a master regulator of cargo retrieval from endosomes, which is critical for many cellular processes including signaling, immunity, neuroprotection, and virus infection. The retromer core ...Retromer is a master regulator of cargo retrieval from endosomes, which is critical for many cellular processes including signaling, immunity, neuroprotection, and virus infection. The retromer core (VPS26/VPS29/VPS35) is present on cargo-transporting, tubular carriers along with a range of sorting nexins. Here, we elucidate the structural basis of membrane tubulation and coupled cargo recognition by metazoan and fungal retromer coats assembled with the non-Bin1/Amphiphysin/Rvs (BAR) sorting nexin SNX3 using cryo-electron tomography. The retromer core retains its arched, scaffolding structure but changes its mode of membrane recruitment when assembled with different SNX adaptors, allowing cargo recognition at subunit interfaces. Thus, membrane bending and cargo incorporation can be modulated to allow retromer to traffic cargoes along different cellular transport routes.
External linksSci Adv / PubMed:33762348 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution8.9 - 9.5 Å
Structure data

12220

7bln

EMDB-12220: VPS35/VPS29 arch of metazoan membrane-assembled retromer:SNX3 complex
PDB-7bln: VPS35/VPS29 arch of metazoan membrane-assembled retromer:SNX3 complex modelled with human proteins
Method: EM (subtomogram averaging) / Resolution: 8.9 Å

12221

7blo

EMDB-12221: VPS26 dimer region of metazoan membrane-assembled retromer:SNX3 complex
PDB-7blo: VPS26 dimer region of metazoan membrane-assembled retromer:SNX3 complex modelled with human proteins
Method: EM (subtomogram averaging) / Resolution: 9.5 Å

EMDB-12222:
tomogram of membrane tubules coated with metazoan retromer:SNX3 in the presence of Wls cargo.
Method: EM (tomography)

12223

7blp

EMDB-12223, PDB-7blp:
Vps35/Vps29 arch of fungal membrane-assembled retromer:Grd19 complex
Method: EM (subtomogram averaging) / Resolution: 9.5 Å

12224

7blq

EMDB-12224, PDB-7blq:
Vps26 dimer region of the fungal membrane-assembled retromer:Grd19 complex.
Method: EM (subtomogram averaging) / Resolution: 9.2 Å

EMDB-12225:
tomogram of membrane tubules coated with fungal retromer:Grd19 in the presence of Kex2 cargo.
Method: EM (tomography)

12226

7blr

EMDB-12226, PDB-7blr:
Vps35/Vps29 arch of fungal membrane-assembled retromer:Vps5 (SNX-BAR) complex.
Method: EM (subtomogram averaging) / Resolution: 9.3 Å

Chemicals

ChemComp-PIB:
2-(BUTANOYLOXY)-1-{[(HYDROXY{[2,3,4,6-TETRAHYDROXY-5-(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL)OXY]METHYL}ETHYL

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • chaetomium thermophilum var. thermophilum dsm 1495 (fungus)
  • chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
KeywordsENDOCYTOSIS / endosomes / coat proteins / membrane trafficking / cargo-sorting

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