+Open data
-Basic information
Entry | Database: PDB / ID: 7czv | ||||||
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Title | S protein of SARS-CoV-2 in complex bound with P5A-1B6_3B | ||||||
Components |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / antibody | ||||||
Function / homology | Function and homology information positive regulation of B cell activation / phagocytosis, recognition / CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / phagocytosis, engulfment / FCGR activation / Role of phospholipids in phagocytosis ...positive regulation of B cell activation / phagocytosis, recognition / CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / phagocytosis, engulfment / FCGR activation / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / complement activation, classical pathway / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / antigen binding / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated NF-kB activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / antibacterial humoral response / Potential therapeutics for SARS / adaptive immune response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / blood microparticle / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / defense response to bacterium / immune response / external side of plasma membrane / fusion of virus membrane with host plasma membrane / innate immune response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Yan, R.H. / Zhang, Y.Y. / Li, Y.N. / Zhou, Q. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Res / Year: 2021 Title: Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies. Authors: Renhong Yan / Ruoke Wang / Bin Ju / Jinfang Yu / Yuanyuan Zhang / Nan Liu / Jia Wang / Qi Zhang / Peng Chen / Bing Zhou / Yaning Li / Yaping Shen / Shuyuan Zhang / Long Tian / Yingying Guo / ...Authors: Renhong Yan / Ruoke Wang / Bin Ju / Jinfang Yu / Yuanyuan Zhang / Nan Liu / Jia Wang / Qi Zhang / Peng Chen / Bing Zhou / Yaning Li / Yaping Shen / Shuyuan Zhang / Long Tian / Yingying Guo / Lu Xia / Xinyue Zhong / Lin Cheng / Xiangyang Ge / Juanjuan Zhao / Hong-Wei Wang / Xinquan Wang / Zheng Zhang / Linqi Zhang / Qiang Zhou / Abstract: Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 ...Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7czv.cif.gz | 795.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7czv.ent.gz | 651.6 KB | Display | PDB format |
PDBx/mmJSON format | 7czv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7czv_validation.pdf.gz | 2.8 MB | Display | wwPDB validaton report |
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Full document | 7czv_full_validation.pdf.gz | 3 MB | Display | |
Data in XML | 7czv_validation.xml.gz | 140.3 KB | Display | |
Data in CIF | 7czv_validation.cif.gz | 204.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cz/7czv ftp://data.pdbj.org/pub/pdb/validation_reports/cz/7czv | HTTPS FTP |
-Related structure data
Related structure data | 30518MC 7czpC 7czqC 7czrC 7czsC 7cztC 7czuC 7czwC 7czxC 7czyC 7czzC 7d00C 7d03C 7d0bC 7d0cC 7d0dC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 142502.594 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 49987.258 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IGHV3-30-3 / Production host: Homo sapiens (human) / References: UniProt: P0DP02, UniProt: P0DOX5 #3: Antibody | Mass: 23542.959 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IGKV1-33 / Production host: Homo sapiens (human) / References: UniProt: P01594, UniProt: Q8TCD0 #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
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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: S protein of SARS-CoV-2 in complex bound with P5A-1B6_3B Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
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 / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software | Name: RELION / Version: 3.0.6 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55619 / Symmetry type: POINT |