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Yorodumi- PDB-8i3s: Local CryoEM structure of the SARS-CoV-2 S6P in complex with 7B3 Fab -
+Open data
-Basic information
Entry | Database: PDB / ID: 8i3s | ||||||
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Title | Local CryoEM structure of the SARS-CoV-2 S6P in complex with 7B3 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-Cov-2 / receptor binding domain / RBD / Fab / coronavirus / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information 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 / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / 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 / identical protein binding / membrane / 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: 3.9 Å | ||||||
Authors | Li, Z. / Yu, F. / Cao, S. / ZHao, H. | ||||||
Funding support | China, 1items
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Citation | Journal: Signal Transduct Target Ther / Year: 2023 Title: Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge. Authors: Qianyun Liu / Haiyan Zhao / Zhiqiang Li / Zhen Zhang / Rui Huang / Mengxue Gu / Ke Zhuang / Qing Xiong / Xianying Chen / Weiyi Yu / Shengnan Qian / Yuzhen Zhang / Xue Tan / Muyi Zhang / ...Authors: Qianyun Liu / Haiyan Zhao / Zhiqiang Li / Zhen Zhang / Rui Huang / Mengxue Gu / Ke Zhuang / Qing Xiong / Xianying Chen / Weiyi Yu / Shengnan Qian / Yuzhen Zhang / Xue Tan / Muyi Zhang / Feiyang Yu / Ming Guo / Zhixiang Huang / Xin Wang / Wenjie Xiang / Bihao Wu / Fanghua Mei / Kun Cai / Limin Zhou / Li Zhou / Ying Wu / Huan Yan / Sheng Cao / Ke Lan / Yu Chen / Abstract: Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we ...Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8i3s.cif.gz | 115.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8i3s.ent.gz | 69.9 KB | Display | PDB format |
PDBx/mmJSON format | 8i3s.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8i3s_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8i3s_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8i3s_validation.xml.gz | 34.8 KB | Display | |
Data in CIF | 8i3s_validation.cif.gz | 47.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i3/8i3s ftp://data.pdbj.org/pub/pdb/validation_reports/i3/8i3s | HTTPS FTP |
-Related structure data
Related structure data | 35155MC 8i3uC M: map data used to model this data C: citing same article (ref.) |
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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: 137897.609 Da / Num. of mol.: 1 / Fragment: RBD region / Mutation: F817P, A892P, A899P, A942P, K986P, V987P 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 |
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#2: Antibody | Mass: 24534.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 23278.826 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | N |
-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: Spike-Fab complex / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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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
Microscopy | Model: JEOL CRYO ARM 300 |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 86212 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE | ||||||||||||||||||||||||
Refine LS restraints |
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