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Yorodumi- PDB-8keq: State 1 of SARS-CoV-2 XBB Variant Spike protein trimer complexed ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8keq | ||||||
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Title | State 1 of SARS-CoV-2 XBB Variant Spike protein trimer complexed with antibody PW5-5 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / 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 / entry receptor-mediated virion attachment to host cell ...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 / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 / 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: 3.14 Å | ||||||
Authors | Sun, L. / Mao, Q. / Wang, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Discov / Year: 2024 Title: Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination. Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / ...Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / Yuchen Cui / Chaoyue Zhao / Minghui Li / Yanjia Chen / Guonan Cai / Wenye Geng / Zixin Hu / Jinglei Cao / Wenhong Zhang / Zhiwei Cao / Hin Chu / Lei Sun / Pengfei Wang / Abstract: The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the ...The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8keq.cif.gz | 721.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8keq.ent.gz | 572.7 KB | Display | PDB format |
PDBx/mmJSON format | 8keq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8keq_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8keq_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8keq_validation.xml.gz | 107.4 KB | Display | |
Data in CIF | 8keq_validation.cif.gz | 161.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ke/8keq ftp://data.pdbj.org/pub/pdb/validation_reports/ke/8keq | HTTPS FTP |
-Related structure data
Related structure data | 37164MC 8kdmC 8kdrC 8kdsC 8kdtC 8kehC 8kejC 8kekC 8keoC 8kepC 8kerC 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: 143147.531 Da / Num. of mol.: 3 Mutation: R682G, R683S, R685S, F817P, A892P, A899P, A942P, K986P, V987P Source method: isolated from a genetically manipulated source Details: XBB spike Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 49374.523 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 23782.463 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) Has protein modification | 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: XBB spike protein (S) in complex with broadly neutralizing antibody PW5-5 state1 Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
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: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 208476 / Symmetry type: POINT | ||||||||||||||||||||||||
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