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Yorodumi- PDB-6owt: Structure of SIVsmm Nef and SMM tetherin bound to the clathrin ad... -
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-Basic information
Entry | Database: PDB / ID: 6owt | |||||||||
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Title | Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex | |||||||||
Components |
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Keywords | PROTEIN TRANSPORT / AP / HIV / Nef / trafficking / viral restriction factor | |||||||||
Function / homology | Function and homology information AP-type membrane coat adaptor complex / Formation of annular gap junctions / Gap junction degradation / postsynaptic endocytic zone / LDL clearance / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / LDL clearance / WNT5A-dependent internalization of FZD4 / VLDLR internalisation and degradation ...AP-type membrane coat adaptor complex / Formation of annular gap junctions / Gap junction degradation / postsynaptic endocytic zone / LDL clearance / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / LDL clearance / WNT5A-dependent internalization of FZD4 / VLDLR internalisation and degradation / Retrograde neurotrophin signalling / Trafficking of GluR2-containing AMPA receptors / Retrograde neurotrophin signalling / clathrin adaptor complex / WNT5A-dependent internalization of FZD4 / clathrin coat / extrinsic component of presynaptic endocytic zone membrane / VLDLR internalisation and degradation / cardiac septum development / virus-mediated perturbation of host defense response => GO:0019049 / MHC class II antigen presentation / Recycling pathway of L1 / AP-2 adaptor complex / regulation of vesicle size / postsynaptic neurotransmitter receptor internalization / Recycling pathway of L1 / clathrin coat assembly / Cargo recognition for clathrin-mediated endocytosis / Cargo recognition for clathrin-mediated endocytosis / positive regulation of synaptic vesicle endocytosis / Clathrin-mediated endocytosis / clathrin adaptor activity / Clathrin-mediated endocytosis / membrane coat / vesicle budding from membrane / clathrin-dependent endocytosis / MHC class II antigen presentation / coronary vasculature development / positive regulation of protein localization to membrane / neurotransmitter receptor internalization / signal sequence binding / aorta development / negative regulation of protein localization to plasma membrane / ventricular septum development / Neutrophil degranulation / low-density lipoprotein particle receptor binding / clathrin binding / positive regulation of endocytosis / Trafficking of GluR2-containing AMPA receptors / positive regulation of receptor internalization / synaptic vesicle endocytosis / protein serine/threonine kinase binding / vesicle-mediated transport / phosphatidylinositol binding / secretory granule / kidney development / kinase binding / intracellular protein transport / cytoplasmic side of plasma membrane / disordered domain specific binding / synaptic vesicle / presynapse / heart development / cytoplasmic vesicle / protein-containing complex assembly / defense response to virus / transmembrane transporter binding / postsynapse / membrane => GO:0016020 / protein domain specific binding / intracellular membrane-bounded organelle / lipid binding / glutamatergic synapse / synapse / protein-containing complex binding / GTP binding / protein kinase binding / mitochondrion / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) Mus musculus (house mouse) Cercocebus atys (sooty mangabey) Simian immunodeficiency virus | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Buffalo, C.Z. / Ren, X. / Hurley, J.H. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell Host Microbe / Year: 2019 Title: Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission. Authors: Cosmo Z Buffalo / Christina M Stürzel / Elena Heusinger / Dorota Kmiec / Frank Kirchhoff / James H Hurley / Xuefeng Ren / Abstract: Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 ...Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
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PDBx/mmCIF format | 6owt.cif.gz | 286.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6owt.ent.gz | 222.9 KB | Display | PDB format |
PDBx/mmJSON format | 6owt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6owt_validation.pdf.gz | 742.4 KB | Display | wwPDB validaton report |
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Full document | 6owt_full_validation.pdf.gz | 752.5 KB | Display | |
Data in XML | 6owt_validation.xml.gz | 47.9 KB | Display | |
Data in CIF | 6owt_validation.cif.gz | 73.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ow/6owt ftp://data.pdbj.org/pub/pdb/validation_reports/ow/6owt | HTTPS FTP |
-Related structure data
Related structure data | 20217MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 104286.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Ap2a2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q66HM2, UniProt: P18484*PLUS | ||
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#2: Protein | Mass: 66953.195 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Ap2b1, Clapb1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62944 | ||
#3: Protein | Mass: 16161.563 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ap2m1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q5FWI9, UniProt: P84091*PLUS | ||
#4: Protein | Mass: 31772.352 Da / Num. of mol.: 2 / Mutation: C55A Source method: isolated from a genetically manipulated source Details: protein chimera of the cytoplasmic tail of sooty mangabey (smm) linked to the N-terminus of SIV smm tetherin Source: (gene. exp.) Cercocebus atys (sooty mangabey), (gene. exp.) Simian immunodeficiency virus Gene: BST2, nef / Production host: Escherichia coli (E. coli) / References: UniProt: C3VHQ5, UniProt: Q4JGV0 #5: Protein | | Mass: 17011.662 Da / Num. of mol.: 1 / Mutation: N97C, C99S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Ap2s1, Ap17, Claps2 / Production host: Escherichia coli (E. coli) / References: UniProt: P62744 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.2036 MDa / Experimental value: YES |
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: 25mA / Grid type: C-flat-2/1 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50.16 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.15_3459: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 159406 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building |
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Refine LS restraints |
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