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- EMDB-6542: Structure of Simian Immunodeficiency Virus Envelope Spikes bound ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-6542 | |||||||||
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Title | Structure of Simian Immunodeficiency Virus Envelope Spikes bound with CD4 and Monoclonal Antibody 36D5 | |||||||||
![]() | Reconstruction of closed state SIV envelope spike bound with CD4 and 36D5 | |||||||||
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![]() | Cryoelectron tomography / image processing / electron microscopy / immunology / AIDS / HIV | |||||||||
Function / homology | ![]() helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / regulation of T cell activation / extracellular matrix structural constituent / T cell receptor complex / Other interleukin signaling / enzyme-linked receptor protein signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / regulation of calcium ion transport / macrophage differentiation / Generation of second messenger molecules / T cell differentiation / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / cell surface receptor protein tyrosine kinase signaling pathway / T cell activation / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / protein tyrosine kinase binding / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of T cell activation / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / MHC class II protein complex binding / Clathrin-mediated endocytosis / virus receptor activity / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / positive regulation of viral entry into host cell / early endosome / cell surface receptor signaling pathway / cell adhesion / immune response / positive regulation of protein phosphorylation / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / protein kinase binding / positive regulation of DNA-templated transcription / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | subtomogram averaging / cryo EM | |||||||||
![]() | Hu G / Liu J / Roux KH / Taylor KA | |||||||||
![]() | ![]() Title: Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5. Authors: Guiqing Hu / Jun Liu / Kenneth H Roux / Kenneth A Taylor / ![]() Abstract: The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer ...The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the rapid freezing step, which were separated using statistical analysis. Our results show that the CD4-induced conformational dynamics of the spike enhances binding of the antibody. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 265.4 KB | ![]() | |
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Header (meta data) | ![]() ![]() | 9.6 KB 9.6 KB | Display Display | ![]() |
Images | ![]() | 71.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3jcbMC ![]() 6538C ![]() 6539C ![]() 6540C ![]() 6541C ![]() 6543C ![]() 3jccC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Reconstruction of closed state SIV envelope spike bound with CD4 and 36D5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 5.7 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : SIV envelope bound to CD4 and monoclonal antibody 36D5 in closed state
Entire | Name: SIV envelope bound to CD4 and monoclonal antibody 36D5 in closed state |
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Components |
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-Supramolecule #1000: SIV envelope bound to CD4 and monoclonal antibody 36D5 in closed state
Supramolecule | Name: SIV envelope bound to CD4 and monoclonal antibody 36D5 in closed state type: sample / ID: 1000 Oligomeric state: gp120 trimer bound to CD4 and one antibody 36D5 Number unique components: 3 |
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-Supramolecule #1: Simian immunodeficiency virus
Supramolecule | Name: Simian immunodeficiency virus / type: virus / ID: 1 / Name.synonym: SIV / NCBI-ID: 11723 / Sci species name: Simian immunodeficiency virus / Sci species strain: SIV239/251tail/Supt-CCR5 CL.30 / Database: NCBI / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No / Syn species name: SIV |
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Host (natural) | Organism: ![]() |
-Macromolecule #1: T-cell surface glycoprotein CD4
Macromolecule | Name: T-cell surface glycoprotein CD4 / type: protein_or_peptide / ID: 1 / Name.synonym: CD4 / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: ![]() |
-Macromolecule #2: monoclonal antibody 36D5
Macromolecule | Name: monoclonal antibody 36D5 / type: protein_or_peptide / ID: 2 / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: ![]() ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | subtomogram averaging |
Aggregation state | particle |
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Sample preparation
Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Date | Aug 16, 2008 |
Image recording | Category: CCD / Film or detector model: TVIPS TEMCAM-F415 (4k x 4k) / Average electron dose: 100 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 4.0 µm / Nominal magnification: 31000 |
Sample stage | Specimen holder: cryo holder / Specimen holder model: OTHER / Tilt series - Axis1 - Min angle: -65 ° / Tilt series - Axis1 - Max angle: 65 ° |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Software - Name: I3, protomo / Number subtomograms used: 1181 |
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