6H7W

Model of retromer-Vps5 complex assembled on membrane.


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 11.4 Å
  • Aggregation State: 3D ARRAY 
  • Reconstruction Method: SUBTOMOGRAM AVERAGING 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of the membrane-assembled retromer coat determined by cryo-electron tomography.

Kovtun, O.Leneva, N.Bykov, Y.S.Ariotti, N.Teasdale, R.D.Schaffer, M.Engel, B.D.Owen, D.J.Briggs, J.A.G.Collins, B.M.

(2018) Nature 561: 561-564

  • DOI: https://doi.org/10.1038/s41586-018-0526-z
  • Primary Citation of Related Structures:  
    5W8M, 6H7W

  • PubMed Abstract: 

    Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes 1-3 . Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders 4-7 . How retromer is assembled and how it is recruited to form coated tubules is not known. Here we describe the structure of the retromer complex (Vps26-Vps29-Vps35) assembled on membrane tubules with the bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo-electron tomography and subtomogram averaging. This reveals a membrane-associated Vps5 array, from which arches of retromer extend away from the membrane surface. Vps35 forms the 'legs' of these arches, and Vps29 resides at the apex where it is free to interact with regulatory factors. The bases of the arches connect to each other and to Vps5 through Vps26, and the presence of the same arches on coated tubules within cells confirms their functional importance. Vps5 binds to Vps26 at a position analogous to the previously described cargo- and Snx3-binding site, which suggests the existence of distinct retromer-sorting nexin assemblies. The structure provides insight into the architecture of the coat and its mechanism of assembly, and suggests that retromer promotes tubule formation by directing the distribution of sorting nexin proteins on the membrane surface while providing a scaffold for regulatory-protein interactions.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vacuolar protein sorting-associated protein 26-like proteinA [auth J],
B [auth C]
292Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0009750
UniProt
Find proteins for G0S0E6 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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Go to UniProtKB:  G0S0E6
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupG0S0E6
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Putative vacuolar protein sorting-associated protein368Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0068290
UniProt
Find proteins for G0SH11 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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UniProt GroupG0SH11
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Putative vacuolar protein sorting-associated proteinE [auth D],
H [auth K],
O [auth V],
P [auth L]
129Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0068290
UniProt
Find proteins for G0SH11 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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UniProt GroupG0SH11
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Putative vacuolar protein sorting-associated proteinI [auth O],
K [auth M]
220Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0068290
UniProt
Find proteins for G0SH11 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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UniProt GroupG0SH11
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  • Reference Sequence
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Vacuolar protein sorting-associated protein 29Q [auth S],
S [auth T]
193Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0002370
UniProt
Find proteins for G0RZB5 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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UniProt GroupG0RZB5
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Vacuolar protein sorting-associated protein 35R [auth Q],
T [auth R]
846Thermochaetoides thermophila DSM 1495Mutation(s): 0 
Gene Names: CTHT_0035730
Membrane Entity: Yes 
UniProt
Find proteins for G0S709 (Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719))
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UniProt GroupG0S709
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 11.4 Å
  • Aggregation State: 3D ARRAY 
  • Reconstruction Method: SUBTOMOGRAM AVERAGING 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTNAMD

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMC_UP_1201/16
Wellcome TrustUnited Kingdom207455/Z/17/Z
Australian Research CouncilAustraliaDP160101743
National Health and Medical Research Council (Australia)AustraliaAPP1042082
National Health and Medical Research Council (Australia)AustraliaAPP1058734
National Health and Medical Research Council (Australia)AustraliaAPP1041929
National Health and Medical Research Council (Australia)AustraliaAPP1136021

Revision History  (Full details and data files)

  • Version 1.0: 2018-09-26
    Type: Initial release
  • Version 1.1: 2018-10-10
    Changes: Data collection, Database references
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references