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Yorodumi- PDB-8dv1: SARS-CoV-2 Wuhan-hu-1-Spike-RBD bound to linker variant of affini... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dv1 | ||||||||||||
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Title | SARS-CoV-2 Wuhan-hu-1-Spike-RBD bound to linker variant of affinity matured ACE2 mimetic CVD432 | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/ANTIVIRAL PROTEIN / SARS-CoV-2 / Spike / Receptor-binding domain / ACE2 receptor traps / ANTIVIRAL PROTEIN / VIRAL PROTEIN-ANTIVIRAL PROTEIN 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 / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / 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 / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / immunoglobulin complex, circulating / immunoglobulin receptor binding / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / complement activation, classical pathway / negative regulation of smooth muscle cell proliferation / antigen binding / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of inflammatory response / regulation of cell population proliferation / antibacterial humoral response / endopeptidase activity / Potential therapeutics for SARS / 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 / blood microparticle / 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 / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / apical plasma membrane / symbiont entry into host cell / 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 / zinc ion binding / extracellular exosome / 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: 3.4 Å | ||||||||||||
Authors | QCRG Structural Biology Consortium / Remesh, S.G. / Merz, G.E. / Brilot, A.F. / Chio, U. / Verba, K.A. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Structure / Year: 2023 Title: Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps. Authors: Soumya G Remesh / Gregory E Merz / Axel F Brilot / Un Seng Chio / Alexandrea N Rizo / Thomas H Pospiech / Irene Lui / Mathew T Laurie / Jeff Glasgow / Chau Q Le / Yun Zhang / Devan Diwanji / ...Authors: Soumya G Remesh / Gregory E Merz / Axel F Brilot / Un Seng Chio / Alexandrea N Rizo / Thomas H Pospiech / Irene Lui / Mathew T Laurie / Jeff Glasgow / Chau Q Le / Yun Zhang / Devan Diwanji / Evelyn Hernandez / Jocelyne Lopez / Hevatib Mehmood / Komal Ishwar Pawar / Sergei Pourmal / Amber M Smith / Fengbo Zhou / / Joseph DeRisi / Tanja Kortemme / Oren S Rosenberg / Anum Glasgow / Kevin K Leung / James A Wells / Kliment A Verba / Abstract: The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor-binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently ...The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor-binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-RBD and prevent viral entry into host cells ("receptor traps"). Here we determine cryo-EM structures of our receptor traps in complex with stabilized Spike ectodomain. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high-affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high-affinity (0.53-4.2 nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron and Delta pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dv1.cif.gz | 201.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dv1.ent.gz | 143.2 KB | Display | PDB format |
PDBx/mmJSON format | 8dv1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dv1_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8dv1_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8dv1_validation.xml.gz | 41.5 KB | Display | |
Data in CIF | 8dv1_validation.cif.gz | 60.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dv/8dv1 ftp://data.pdbj.org/pub/pdb/validation_reports/dv/8dv1 | HTTPS FTP |
-Related structure data
Related structure data | 27730MC 8dv2C 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: 133753.250 Da / Num. of mol.: 1 / Mutation: R682G, R683S, R685S, K986P, V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Escherichia coli (E. coli) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 110531.703 Da / Num. of mol.: 1 / Mutation: K31F,N33D,H34S,E35Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Production host: Escherichia coli (E. coli) References: UniProt: Q9BYF1, UniProt: P0DOX5, angiotensin-converting enzyme 2, Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases |
#3: Sugar | ChemComp-NAG / |
-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 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 66 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 3 / Num. of real images: 10685 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97082 / Symmetry type: POINT |