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Yorodumi- PDB-7y9z: Cryo-EM structure of SARS-CoV-2 Omicron spike protein (S-6P-RRAR)... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7y9z | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 Omicron spike protein (S-6P-RRAR) in complex with human ACE2 ectodomain (one-RBD-up state) | ||||||
Components |
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Keywords | VIRAL PROTEIN/HYDROLASE / Omicron / ACE2 / SARS-CoV-2 / one RBD up / VIRUS / VIRAL PROTEIN-HYDROLASE complex | ||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / angiotensin maturation / maternal process involved in female pregnancy / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / Attachment and Entry / carboxypeptidase activity / negative regulation of signaling receptor activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / cilium / negative regulation of ERK1 and ERK2 cascade / endocytic vesicle membrane / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / endopeptidase activity / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / Potential therapeutics for SARS / 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 / symbiont entry into host cell / membrane raft / apical plasma membrane / fusion of virus membrane with host plasma membrane / endoplasmic reticulum lumen / 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 / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / 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: 2.85 Å | ||||||
Authors | Gao, G.F. / Qi, J.X. / Liu, S. / Zhao, Z.N. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape. Authors: Zhennan Zhao / Jingya Zhou / Mingxiong Tian / Min Huang / Sheng Liu / Yufeng Xie / Pu Han / Chongzhi Bai / Pengcheng Han / Anqi Zheng / Lutang Fu / Yuanzhu Gao / Qi Peng / Ying Li / Yan Chai ...Authors: Zhennan Zhao / Jingya Zhou / Mingxiong Tian / Min Huang / Sheng Liu / Yufeng Xie / Pu Han / Chongzhi Bai / Pengcheng Han / Anqi Zheng / Lutang Fu / Yuanzhu Gao / Qi Peng / Ying Li / Yan Chai / Zengyuan Zhang / Xin Zhao / Hao Song / Jianxun Qi / Qihui Wang / Peiyi Wang / George F Gao / Abstract: Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its ...Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7y9z.cif.gz | 688.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7y9z.ent.gz | 564.5 KB | Display | PDB format |
PDBx/mmJSON format | 7y9z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y9/7y9z ftp://data.pdbj.org/pub/pdb/validation_reports/y9/7y9z | HTTPS FTP |
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-Related structure data
Related structure data | 33697MC 7y9sC 7ya0C 7ya1C 7yadC 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: 139753.344 Da / Num. of mol.: 3 / Mutation: K986P, V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Protein | | Mass: 69038.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Production host: Homo sapiens (human) / References: UniProt: Q9BYF1 #3: 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 #4: Sugar | ChemComp-NAG / #5: Chemical | ChemComp-ZN / | 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
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Source (natural) |
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Source (recombinant) |
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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: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71507 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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