|Entry||Database: PDB / ID: 3jcb|
|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||helper T cell enhancement of adaptive immune response / T-cell surface antigen CD4 / interleukin-16 binding / interleukin-16 receptor activity / CD4, extracellular / T cell CD4 receptor C-terminal region / induction by virus of host cell-cell fusion / T cell CD4 receptor C terminal region / CD4, extracellular / maintenance of protein location in cell ...helper T cell enhancement of adaptive immune response / T-cell surface antigen CD4 / interleukin-16 binding / interleukin-16 receptor activity / CD4, extracellular / T cell CD4 receptor C-terminal region / induction by virus of host cell-cell fusion / T cell CD4 receptor C terminal region / CD4, extracellular / maintenance of protein location in cell / Immunoglobulin C2-set / regulation of T cell activation / T cell selection / MHC class II protein binding / immunoglobulin binding / extracellular matrix structural constituent / Immunoglobulin C2-set domain / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / positive regulation of kinase activity / response to vitamin D / T cell receptor complex / positive regulation of viral entry into host cell / Alpha-defensins / 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 / cellular response to granulocyte macrophage colony-stimulating factor stimulus / coreceptor activity / Other interleukin signaling / T cell differentiation / regulation of calcium ion transport / cytokine production / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / Immunoglobulin / protein tyrosine kinase binding / PD-1 signaling / Immunoglobulin domain / positive regulation of protein kinase activity / clathrin-coated vesicle membrane / Generation of second messenger molecules / Binding and entry of HIV virion / entry into host cell / positive regulation of T cell proliferation / Vpu mediated degradation of CD4 / transmembrane receptor protein tyrosine kinase signaling pathway / Immunoglobulin subtype 2 / regulation of defense response to virus by virus / transmembrane signaling receptor activity / Cargo recognition for clathrin-mediated endocytosis / virus receptor activity / T cell costimulation / Clathrin-mediated endocytosis / Downstream TCR signaling / Immunoglobulin V-set domain / go:0004872: / membrane organization / adaptive immune response / positive regulation of MAPK cascade / response to estradiol / fusion of virus membrane with host plasma membrane / early endosome / positive regulation of peptidyl-tyrosine phosphorylation / T cell receptor signaling pathway / Immunoglobulin subtype / positive regulation of I-kappaB kinase/NF-kappaB signaling / 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 / external side of plasma membrane / membrane raft / endoplasmic reticulum lumen / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / cytokine-mediated signaling pathway / endoplasmic reticulum membrane / protein kinase binding / positive regulation of transcription, DNA-templated / integral component of plasma membrane / Immunoglobulin-like fold / signal transduction / enzyme binding / 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 / virus / |
Homo sapiens / human /
|Method||Electron microscopy (Cell / Tomography) / Transmission electron microscopy|
|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.
Copyright: 2017 American Society for Microbiology.
SummaryFull reportAbout validation report
|Date||Deposition: Nov 25, 2015 / Release: May 10, 2017|
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 / 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: 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 FIELD / 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: 1181 / 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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