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Yorodumi- PDB-8d5c: anti-HIV-1 gp120-sCD4 complex antibody CG10 Fab in complex with B... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8d5c | |||||||||
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Title | anti-HIV-1 gp120-sCD4 complex antibody CG10 Fab in complex with B41-sCD4 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / HIV-1 Env / anti-HIV-1 antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | |||||||||
Function / homology | Function and homology information 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 / T cell differentiation / Generation of second messenger molecules / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / T cell activation / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / positive regulation of T cell activation / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / MHC class II protein complex binding / Clathrin-mediated endocytosis / signaling receptor activity / virus receptor activity / clathrin-dependent endocytosis of virus by host cell / defense response to Gram-negative bacterium / positive regulation of canonical NF-kappaB signal transduction / adaptive immune response / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / early endosome / positive regulation of viral entry into host cell / cell surface receptor signaling pathway / viral protein processing / cell adhesion / immune response / positive regulation of protein phosphorylation / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / virion attachment to host cell / apoptotic process / protein kinase binding / host cell plasma membrane / positive regulation of DNA-templated transcription / virion membrane / structural molecule activity / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Human immunodeficiency virus Homo sapiens (human) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Yang, Z. / Bjorkman, P.J. / Gershoni, J.M. | |||||||||
Funding support | United States, 2items
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Citation | Journal: J Virol / Year: 2022 Title: Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers. Authors: Zhi Yang / Kim-Marie A Dam / Jonathan M Gershoni / Susan Zolla-Pazner / Pamela J Bjorkman / Abstract: Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 ...Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 and a coreceptor. CD4 binding induces rearrangements in Env trimer, resulting in a CD4-induced (CD4i) open Env conformation. Structural studies of antibodies isolated from infected donors have defined antibody-Env interactions, with one class of antibodies specifically recognizing the CD4i open Env conformation. In this study, we characterized a group of monoclonal antibodies isolated from HIV-1 infected donors (V2i MAbs) that displayed characteristics of CD4i antibodies. Binding experiments demonstrated that the V2i MAbs preferentially recognize CD4-bound open Env trimers. Structural characterizations of V2i MAb-Env-CD4 trimer complexes using single-particle cryo-electron microscopy showed recognition by V2i MAbs using different angles of approach to the gp120 V1V2 domain and the β2/β3 strands on a CD4i open conformation Env with no direct interactions of the MAbs with CD4. We also characterized CG10, a CD4i antibody that was raised in mice immunized with a gp120-CD4 complex, bound to an Env trimer plus CD4. CG10 exhibited characteristics similar to those of the V2i antibodies, i.e., recognition of the open Env conformation, but showed direct contacts to both CD4 and gp120. Structural comparisons of these and previously characterized CD4i antibody interactions with Env provide a suggested mechanism for how these antibodies are elicited during HIV-1 infection. The RV144 HIV-1 clinical vaccination trial showed modest protection against viral infection. Antibody responses to the V1V2 region of HIV-1 Env gp120 were correlated inversely with the risk of infection, and data from three other clinical vaccine trials suggested a similar signal. In addition, antibodies targeting V1V2 have been correlated with protections from simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infections in nonhuman primates. We structurally characterized V2i antibodies directed against V1V2 isolated from HIV-1 infected humans in complex with open Env trimers bound to the host receptor CD4. We also characterized a CD4i antibody that interacts with CD4 as well as the gp120 subunit of an open Env trimer. Our study suggests how V2i and CD4i antibodies were elicited during HIV-1 infection. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8d5c.cif.gz | 569.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8d5c.ent.gz | 469.3 KB | Display | PDB format |
PDBx/mmJSON format | 8d5c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8d5c_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8d5c_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8d5c_validation.xml.gz | 92.6 KB | Display | |
Data in CIF | 8d5c_validation.cif.gz | 135.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d5/8d5c ftp://data.pdbj.org/pub/pdb/validation_reports/d5/8d5c | HTTPS FTP |
-Related structure data
Related structure data | 27208MC 8d54C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 17357.824 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Gene: env / Cell line (production host): CHO Flp-In (Invitrogen) / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UEZ6 #2: Protein | Mass: 57702.469 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus / Gene: env / Cell line (production host): CHO / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UES2 #3: Protein | Mass: 20288.055 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD4 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P01730 #4: Antibody | Mass: 24583.389 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) #5: Antibody | Mass: 23733.164 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) |
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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 |
-Sample preparation
Component | Name: CG10-B41 SOSIP-sCD4 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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 / Nominal defocus max: 3000 nm / Nominal defocus min: 1800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134746 / Symmetry type: POINT |