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Yorodumi- PDB-7mjn: Cryo-EM structure of the SARS-CoV-2 N501Y mutant spike protein ec... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7mjn | |||||||||
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Title | Cryo-EM structure of the SARS-CoV-2 N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) | |||||||||
Components |
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Keywords | VIRAL PROTEIN/Hydrolase / SARS-CoV-2 / glycoprotein / fusion protein / viral protein / ACE2 / 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 / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction ...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 / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / negative regulation of signaling receptor activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / positive regulation of reactive oxygen species metabolic process / metallopeptidase activity / endocytic vesicle membrane / regulation of cell population proliferation / virus receptor activity / regulation of inflammatory response / endopeptidase activity / 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 / Potential therapeutics for SARS / 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 / symbiont entry into host cell / apical plasma membrane / membrane raft / endoplasmic reticulum lumen / 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 / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / 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: 3.29 Å | |||||||||
Authors | Zhu, X. / Mannar, D. / Srivastava, S.S. / Berezuk, A.M. / Demers, J.P. / Saville, J.W. / Leopold, K. / Li, W. / Dimitrov, D.S. / Tuttle, K.S. ...Zhu, X. / Mannar, D. / Srivastava, S.S. / Berezuk, A.M. / Demers, J.P. / Saville, J.W. / Leopold, K. / Li, W. / Dimitrov, D.S. / Tuttle, K.S. / Zhou, S. / Chittori, S. / Subramaniam, S. | |||||||||
Funding support | Canada, 2items
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Citation | Journal: PLoS Biol / Year: 2021 Title: Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. Authors: Xing Zhu / Dhiraj Mannar / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / James W Saville / Karoline Leopold / Wei Li / Dimiter S Dimitrov / Katharine S Tuttle / Steven Zhou ...Authors: Xing Zhu / Dhiraj Mannar / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / James W Saville / Karoline Leopold / Wei Li / Dimiter S Dimitrov / Katharine S Tuttle / Steven Zhou / Sagar Chittori / Sriram Subramaniam / Abstract: The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We ...The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments. | |||||||||
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 | 7mjn.cif.gz | 179.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mjn.ent.gz | 130.2 KB | Display | PDB format |
PDBx/mmJSON format | 7mjn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mjn_validation.pdf.gz | 774.1 KB | Display | wwPDB validaton report |
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Full document | 7mjn_full_validation.pdf.gz | 776 KB | Display | |
Data in XML | 7mjn_validation.xml.gz | 32.6 KB | Display | |
Data in CIF | 7mjn_validation.cif.gz | 48.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mj/7mjn ftp://data.pdbj.org/pub/pdb/validation_reports/mj/7mjn | HTTPS FTP |
-Related structure data
Related structure data | 23879MC 7mjgC 7mjhC 7mjiC 7mjjC 7mjkC 7mjlC 7mjmC 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: 142476.500 Da / Num. of mol.: 1 / Mutation: N501Y 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: Protein | Mass: 70386.992 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: 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: SARS-CoV-2 N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain Type: COMPLEX / Entity ID: #1-#2 / 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 |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
Software |
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EM software | Name: cryoSPARC / Category: final Euler assignment | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 194473 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 150.77 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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