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Yorodumi- PDB-8h7z: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 f... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8h7z | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement) | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / 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 / 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 / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein 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: 3.07 Å | ||||||
Authors | Liu, Z. / Yan, A. / Gao, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants. Authors: Yanqun Wang / An Yan / Deyong Song / Maoqin Duan / Chuangchuang Dong / Jiantao Chen / Zihe Jiang / Yuanzhu Gao / Muding Rao / Jianxia Feng / Zhaoyong Zhang / Ruxi Qi / Xiaomin Ma / Hong Liu ...Authors: Yanqun Wang / An Yan / Deyong Song / Maoqin Duan / Chuangchuang Dong / Jiantao Chen / Zihe Jiang / Yuanzhu Gao / Muding Rao / Jianxia Feng / Zhaoyong Zhang / Ruxi Qi / Xiaomin Ma / Hong Liu / Beibei Yu / Qiaoping Wang / Mengqi Zong / Jie Jiao / Pingping Xing / Rongrong Pan / Dan Li / Juxue Xiao / Junbo Sun / Ying Li / Linfeng Zhang / Zhenduo Shen / Baiping Sun / Yanyan Zhao / Lu Zhang / Jun Dai / Jingxian Zhao / Lan Wang / Changlin Dou / Zheng Liu / Jincun Zhao / Abstract: The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. ...The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8h7z.cif.gz | 126 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8h7z.ent.gz | 93.9 KB | Display | PDB format |
PDBx/mmJSON format | 8h7z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h7/8h7z ftp://data.pdbj.org/pub/pdb/validation_reports/h7/8h7z | HTTPS FTP |
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-Related structure data
Related structure data | 34526MC 8h7lC 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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-Components
#1: Protein | Mass: 22282.211 Da / Num. of mol.: 1 / Fragment: RBD Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 49838.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 23431.002 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
-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: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement) Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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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 FIELDBright-field microscopy / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 1.39 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 361436 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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