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- PDB-6d84: Structure of the cargo bound AP-1:Arf1:tetherin-Nef (L164A, L165A... -
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Basic information
Entry | Database: PDB / ID: 6d84 | ||||||
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Title | Structure of the cargo bound AP-1:Arf1:tetherin-Nef (L164A, L165A) dileucine mutant dimer | ||||||
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![]() | PROTEIN TRANSPORT / AP / HIV / Nef / trafficking | ||||||
Function / homology | ![]() negative regulation of plasmacytoid dendritic cell cytokine production / negative regulation of intracellular transport of viral material / response to interferon-beta / basolateral protein secretion / perturbation by virus of host immune response / negative regulation of CD4 production / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex ...negative regulation of plasmacytoid dendritic cell cytokine production / negative regulation of intracellular transport of viral material / response to interferon-beta / basolateral protein secretion / perturbation by virus of host immune response / negative regulation of CD4 production / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex / Lysosome Vesicle Biogenesis / platelet dense granule organization / protein trimerization / regulation of receptor internalization / Glycosphingolipid transport / response to interferon-alpha / melanosome assembly / regulation of Arp2/3 complex-mediated actin nucleation / symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I / Intra-Golgi traffic / metalloendopeptidase inhibitor activity / Golgi to vacuole transport / symbiont-mediated suppression of host apoptosis / symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II / Synthesis of PIPs at the Golgi membrane / Golgi Associated Vesicle Biogenesis / clathrin adaptor activity / suppression by virus of host autophagy / MHC class II antigen presentation / positive regulation of leukocyte proliferation / CD4 receptor binding / Nef Mediated CD4 Down-regulation / thioesterase binding / dendritic spine organization / determination of left/right symmetry / long-term synaptic depression / clathrin-coated vesicle / COPI-dependent Golgi-to-ER retrograde traffic / azurophil granule membrane / Lysosome Vesicle Biogenesis / clathrin binding / negative regulation of viral genome replication / Golgi Associated Vesicle Biogenesis / B cell activation / cell leading edge / response to type II interferon / host cell Golgi membrane / MHC class I protein binding / Synthesis of PIPs at the plasma membrane / intracellular copper ion homeostasis / protein targeting / side of membrane / COPI-mediated anterograde transport / clathrin-coated pit / vesicle-mediated transport / regulation of calcium-mediated signaling / viral life cycle / MHC class II antigen presentation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / Neutrophil degranulation / sarcomere / multivesicular body / negative regulation of cell migration / small monomeric GTPase / trans-Golgi network membrane / Nef mediated downregulation of MHC class I complex cell surface expression / kidney development / virion component / regulation of actin cytoskeleton organization / intracellular protein transport / response to virus / cytoplasmic vesicle membrane / trans-Golgi network / negative regulation of cell growth / cellular response to virus / SH3 domain binding / SARS-CoV-1 activates/modulates innate immune responses / Interferon alpha/beta signaling / heart development / ATPase binding / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / postsynaptic density / early endosome / neuron projection / membrane raft / apical plasma membrane / protein domain specific binding / lysosomal membrane / Golgi membrane / intracellular membrane-bounded organelle / innate immune response / focal adhesion / signaling receptor binding / GTPase activity / Neutrophil degranulation / GTP binding / protein kinase binding / host cell plasma membrane / perinuclear region of cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.72 Å | ||||||
![]() | Buffalo, C.Z. / Morris, K.L. / Hurley, J.H. | ||||||
Funding support | ![]()
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![]() | ![]() Title: HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation. Authors: Kyle L Morris / Cosmo Z Buffalo / Christina M Stürzel / Elena Heusinger / Frank Kirchhoff / Xuefeng Ren / James H Hurley / ![]() ![]() Abstract: The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, ...The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, HIV-1 Nef, and the cytosolic tail of the restriction factor tetherin suggested a mechanism for inactivating tetherin by Golgi retention. The 4.3 Å structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. HDX-MS and mutational analysis were used to show how cargo dynamics leads to alternative Arf1 trimerization, directing Nef targets to be either retained at the trans-Golgi or sorted to lysosomes. Phosphorylation of the NL4-3 M-Nef was shown to regulate AP-1 trimerization, explaining how O-Nefs lacking this phosphosite counteract tetherin but most M-Nefs do not. These observations show how the higher-order organization of a vesicular coat can be allosterically modulated to direct cargoes to distinct fates. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 753.6 KB | Display | ![]() |
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PDB format | ![]() | 607.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 108.7 KB | Display | |
Data in CIF | ![]() | 163.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7454MC ![]() 7453C ![]() 7455C ![]() 7456C ![]() 7457C ![]() 7458C ![]() 7563C ![]() 6cm9C ![]() 6criC ![]() 6d83C ![]() 6dffC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 8 molecules TLROCHIN
#1: Protein | Mass: 29880.166 Da / Num. of mol.: 4 Fragment: Tetherin UNP residues 2-21, Nef UNP residues 1-206 Mutation: L164A, L165A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: BST2, nef / Production host: ![]() ![]() #3: Protein | Mass: 22314.250 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-AP-1 complex subunit ... , 4 types, 8 molecules BFGKMPSQ
#2: Protein | Mass: 66152.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 68194.094 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #5: Protein | Mass: 48606.730 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #6: Protein | Mass: 18321.338 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 2 types, 8 molecules ![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
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#7: Chemical | ChemComp-GTP / #8: Chemical | ChemComp-MG / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Structure of the HIV-Nef(163A,165A) tetherin cargo bound AP1:Arf1 dimer Type: COMPLEX / Entity ID: #2-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 39.7 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 6.72 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42902 / Symmetry type: POINT | ||||||||||||||||||||||||
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