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- EMDB-24778: Cryo-EM structure of the SARS-CoV-2 HR1HR2 fusion core complex wi... -
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Open data
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Basic information
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Title | Cryo-EM structure of the SARS-CoV-2 HR1HR2 fusion core complex with A942S mutation | |||||||||
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![]() | spike / HR1HR2 / fusion / A942S / VIRAL PROTEIN | |||||||||
Function / homology | ![]() oxidoreductase activity, acting on metal ions / ferric iron binding / 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 ...oxidoreductase activity, acting on metal ions / ferric iron binding / 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 / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||
![]() | Yang K / Brunger AT | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle. Authors: Kailu Yang / Chuchu Wang / K Ian White / Richard A Pfuetzner / Luis Esquivies / Axel T Brunger / ![]() Abstract: Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the ...Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus–host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2–3.8 Å resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme. This molecular scaffold enables efficient sample preparation and structure determination of the HR1HR2 bundle and its mutants by single-particle cryo-EM. Our structure of the wild-type HR1HR2 bundle resolves uncertainties in previously determined structures. The mutant structures reveal side-chain positions of the mutations and their primarily local effects on the interactions between HR1 and HR2. These mutations do not alter the global architecture of the postfusion HR1HR2 bundle, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors that should be efficacious against all known variants of SARS-CoV-2 to date. We also note that this work paves the way for similar studies in more distantly related viruses. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.6 KB 10.6 KB | Display Display | ![]() |
Images | ![]() | 63.2 KB | ||
Filedesc metadata | ![]() | 5.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rzuMC ![]() 7rzqC ![]() 7rzrC ![]() 7rzsC ![]() 7rztC ![]() 7rzvC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.81625 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : SARS-CoV-2 HR1HR2 complex with A942S mutation
Entire | Name: SARS-CoV-2 HR1HR2 complex with A942S mutation |
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Components |
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-Supramolecule #1: SARS-CoV-2 HR1HR2 complex with A942S mutation
Supramolecule | Name: SARS-CoV-2 HR1HR2 complex with A942S mutation / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 40 KDa |
-Macromolecule #1: SARS-CoV-2 HR1 A942S linked to a scaffold,Spike protein S2'
Macromolecule | Name: SARS-CoV-2 HR1 A942S linked to a scaffold,Spike protein S2' type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 28.775055 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSHHHHHHGS QTLLRNFGNV YDNPVLLDRS VTAPVTEGFN VVLASFQALY LQYQKHHFVV EGSEFYSLHE FFNESYNQVQ DHIHEIGER LDGLGGVPVA TFSKLAELTC FEQESEGVYS SRQMVENDLA AEQAIIGVIR RQAAQAESLG DRGTRYLYEK I LLKTEERA ...String: MSHHHHHHGS QTLLRNFGNV YDNPVLLDRS VTAPVTEGFN VVLASFQALY LQYQKHHFVV EGSEFYSLHE FFNESYNQVQ DHIHEIGER LDGLGGVPVA TFSKLAELTC FEQESEGVYS SRQMVENDLA AEQAIIGVIR RQAAQAESLG DRGTRYLYEK I LLKTEERA YHLSHFLAKD SLTLGFAYEN QKLIANQFNS AIGKIQDSLS STSSALGKLQ DVVNQNAQAL NTLVKQLSSN FG AISSVLN DILSRLDKVE UniProtKB: Ferritin, Dps family protein, Spike glycoprotein |
-Macromolecule #2: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 4.422881 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL Q UniProtKB: Spike glycoprotein |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 562936 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |