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- PDB-8fxc: SARS-CoV-2 BQ.1.1 spike RBD bound to the human ACE2 ectodomain an... -
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Basic information
Entry | Database: PDB / ID: 8fxc | ||||||
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Title | SARS-CoV-2 BQ.1.1 spike RBD bound to the human ACE2 ectodomain and the S309 neutralizing antibody Fab fragment | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / COVID-19 / BQ.1.1 / Spike glycoprotein / Neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Inhibitor / ACE2 / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() 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 / 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 / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction / 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 / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / 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 cell population proliferation / 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 / 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 / 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 | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Park, Y.J. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler, D. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Neutralization, effector function and immune imprinting of Omicron variants. Authors: Amin Addetia / Luca Piccoli / James Brett Case / Young-Jun Park / Martina Beltramello / Barbara Guarino / Ha Dang / Guilherme Dias de Melo / Dora Pinto / Kaitlin Sprouse / Suzanne M ...Authors: Amin Addetia / Luca Piccoli / James Brett Case / Young-Jun Park / Martina Beltramello / Barbara Guarino / Ha Dang / Guilherme Dias de Melo / Dora Pinto / Kaitlin Sprouse / Suzanne M Scheaffer / Jessica Bassi / Chiara Silacci-Fregni / Francesco Muoio / Marco Dini / Lucia Vincenzetti / Rima Acosta / Daisy Johnson / Sambhavi Subramanian / Christian Saliba / Martina Giurdanella / Gloria Lombardo / Giada Leoni / Katja Culap / Carley McAlister / Anushka Rajesh / Exequiel Dellota / Jiayi Zhou / Nisar Farhat / Dana Bohan / Julia Noack / Alex Chen / Florian A Lempp / Joel Quispe / Lauriane Kergoat / Florence Larrous / Elisabetta Cameroni / Bradley Whitener / Olivier Giannini / Pietro Cippà / Alessandro Ceschi / Paolo Ferrari / Alessandra Franzetti-Pellanda / Maira Biggiogero / Christian Garzoni / Stephanie Zappi / Luca Bernasconi / Min Jeong Kim / Laura E Rosen / Gretja Schnell / Nadine Czudnochowski / Fabio Benigni / Nicholas Franko / Jennifer K Logue / Courtney Yoshiyama / Cameron Stewart / Helen Chu / Hervé Bourhy / Michael A Schmid / Lisa A Purcell / Gyorgy Snell / Antonio Lanzavecchia / Michael S Diamond / Davide Corti / David Veesler / ![]() ![]() ![]() ![]() Abstract: Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection ...Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 216.9 KB | Display | ![]() |
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PDB format | ![]() | 158.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 29531MC ![]() 8fxbC ![]() 8s9gC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AE
#3: Protein | Mass: 74492.406 Da / Num. of mol.: 1 / Fragment: ectodomain Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Protein | Mass: 28196.900 Da / Num. of mol.: 1 / Fragment: Receptor binding domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() |
-Antibody , 2 types, 2 molecules LH
#1: Antibody | Mass: 23204.697 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Antibody | Mass: 50163.277 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 2 types, 6 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#6: Sugar | ChemComp-NAG / |
-Non-polymers , 1 types, 1 molecules ![](data/chem/img/ZN.gif)
#7: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | N |
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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 |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||
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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 564986 / Symmetry type: POINT |