|Entry||Database: PDB / ID: 3jcc|
|Title||Structure of Simian Immunodeficiency Virus Envelope Spikes bound with CD4 and Monoclonal Antibody 36D5|
|Keywords||VIRAL PROTEIN/IMMUNE SYSTEM / Cryoelectron tomography / immunology / AIDS / HIV / VIRAL PROTEIN-IMMUNE SYSTEM complex|
|Function / homology||Immunoglobulin subtype / Immunoglobulin-like domain superfamily / CD4, extracellular / Immunoglobulin-like fold / Immunoglobulin domain / Immunoglobulin C2-set domain / Immunoglobulin / CD4, extracellular / T cell CD4 receptor C terminal region / Immunoglobulin V-set domain ...Immunoglobulin subtype / Immunoglobulin-like domain superfamily / CD4, extracellular / Immunoglobulin-like fold / Immunoglobulin domain / Immunoglobulin C2-set domain / Immunoglobulin / CD4, extracellular / T cell CD4 receptor C terminal region / Immunoglobulin V-set domain / Immunoglobulin C2-set / Ig-like domain profile. / Alpha-defensins / Immunoglobulin-like domain / Nef Mediated CD4 Down-regulation / Binding and entry of HIV virion / Vpu mediated degradation of CD4 / Downstream TCR signaling / Phosphorylation of CD3 and TCR zeta chains / Translocation of ZAP-70 to Immunological synapse / Generation of second messenger molecules / PD-1 signaling / Other interleukin signaling / Immunoglobulin subtype 2 / T-cell surface antigen CD4 / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / T cell CD4 receptor C-terminal region / helper T cell enhancement of adaptive immune response / interleukin-16 receptor activity / interleukin-16 binding / induction by virus of host cell-cell fusion / maintenance of protein location in cell / T cell selection / regulation of T cell activation / MHC class II protein binding / immunoglobulin binding / extracellular matrix structural constituent / positive regulation of monocyte differentiation / positive regulation of kinase activity / response to vitamin D / T cell receptor complex / positive regulation of viral entry into host cell / interleukin-15-mediated signaling pathway / positive regulation of interleukin-2 biosynthetic process / enzyme linked receptor protein signaling pathway / positive regulation of calcium ion transport into cytosol / positive regulation of calcium-mediated signaling / coreceptor activity / cellular response to granulocyte macrophage colony-stimulating factor stimulus / T cell differentiation / regulation of calcium ion transport / cytokine production / protein tyrosine kinase binding / positive regulation of protein kinase activity / clathrin-coated vesicle membrane / positive regulation of T cell proliferation / entry into host cell / transmembrane receptor protein tyrosine kinase signaling pathway / regulation of defense response to virus by virus / transmembrane signaling receptor activity / signaling receptor activity / virus receptor activity / T cell receptor signaling pathway / membrane organization / adaptive immune response / positive regulation of MAPK cascade / response to estradiol / fusion of virus membrane with host plasma membrane / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of I-kappaB kinase/NF-kappaB signaling / early endosome / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / immune response / defense response to Gram-negative bacterium / positive regulation of protein phosphorylation / cell adhesion / membrane raft / external side of plasma membrane / endoplasmic reticulum lumen / cytokine-mediated signaling pathway / endoplasmic reticulum membrane / protein kinase binding / positive regulation of transcription, DNA-templated / integral component of plasma membrane / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane / T-cell surface glycoprotein CD4|
Function and homology information
|Specimen source||Simian immunodeficiency virus|
Homo sapiens (human)
|Method||ELECTRON MICROSCOPY / electron tomography / cryo EM|
|Authors||Hu, G. / Liu, J. / Roux, K. / Taylor, K.A.|
|Citation||Journal: J. Virol. / Year: 2017|
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.
SummaryFull reportAbout validation report
|Date||Deposition: Nov 25, 2015 / Release: May 10, 2017|
|Structure viewer||Molecule: |
Downloads & links
A: Envelope glycoprotein gp120
B: Antibody 36D5 light chain
C: Antibody 36D5 heavy chain
D: T-cell surface glycoprotein CD4
E: Envelope glycoprotein gp120
I: Envelope glycoprotein gp120
Mass: 50130.594 Da / Num. of mol.: 3 / Fragment: SEE REMARK 999 / Source: (natural) Simian immunodeficiency virus / Strain: SIV239/251tail/Supt-CCR5 CL.30
Mass: 22291.643 Da / Num. of mol.: 1 / Fragment: Fab / Source: (natural) Homo sapiens (human)
Mass: 25115.289 Da / Num. of mol.: 1 / Fragment: Fab / Source: (natural) Homo sapiens (human)
Mass: 19442.045 Da / Num. of mol.: 1 / Fragment: UNP residues 26-200 / Source: (natural) Homo sapiens (human) / References: UniProt: P01730
|Sequence details||ENVELOPE GLYCOPROTE|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: CELL / Reconstruction method: electron tomography|
|Details of virus||Empty: NO / Enveloped: YES / Virus host category: VERTEBRATES / Virus isolate: STRAIN / Virus type: VIRION|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Details: Plunged into liquid ethane.|
-Electron microscopy imaging
Model: Tecnai Polara / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI POLARA 300 / Date: Aug 16, 2008|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 31000 / Nominal defocus max: 5000 nm / Nominal defocus min: 4000 nm|
|Specimen holder||Specimen holder model: OTHER / Specimen holder type: unidentified / Tilt angle max: 65 deg. / Tilt angle min: -65 deg.|
|Image recording||Electron dose: 100 e/Å2 / Film or detector model: TVIPS TEMCAM-F415 (4k x 4k)|
|Symmetry||Point symmetry: C1|
|3D reconstruction||Number of particles: 1796 / Nominal pixel size: 5.7 / Actual pixel size: 5.7 / Details: (Subtomogram Averaging--Applied Symmetry: C1) / Symmetry type: POINT|
|Atomic model building||Ref protocol: RIGID BODY FIT / Ref space: REAL|
|Atomic model building||PDB-ID: 4NCO|
|Number of atoms included #LAST||Protein: 13909 / Nucleic acid: 0 / Ligand: 0 / Solvent: 0 / Total: 13909|
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