+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33577 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | S-ECD (Omicron BA.3) in complex with two PD of ACE2 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | SARS-Cov-2 / VIRAL PROTEIN / 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 / 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 / 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 / negative regulation of smooth muscle cell proliferation / 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 / 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 / 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 | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Li YN / Shen YP / Zhang YY / Yan RH | |||||||||
Funding support | China, 1 items
| |||||||||
Citation | Journal: Viruses / Year: 2023 Title: Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants. Authors: Yaning Li / Yaping Shen / Yuanyuan Zhang / Renhong Yan / Abstract: The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S ...The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S protein) compared to the original wild-type (WT) strain. Here we report the cryo-EM structures of the trimeric S proteins from the BA.1, BA.2, BA.3, and BA.4/BA.5 subvariants, with BA.4 and BA.5 sharing the same S protein mutations, each in complex with the surface receptor ACE2. All three receptor-binding domains of the S protein from BA.2 and BA.4/BA.5 are "up", while the BA.1 S protein has two "up" and one "down". The BA.3 S protein displays increased heterogeneity, with the majority in the all "up" RBD state. The different conformations preferences of the S protein are consistent with their varied transmissibility. By analyzing the position of the glycan modification on Asn343, which is located at the S309 epitopes, we have uncovered the underlying immune evasion mechanism of the Omicron subvariants. Our findings provide a molecular basis of high infectivity and immune evasion of Omicron subvariants, thereby offering insights into potential therapeutic interventions against SARS-CoV-2 variants. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_33577.map.gz | 86.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-33577-v30.xml emd-33577.xml | 17 KB 17 KB | Display Display | EMDB header |
Images | emd_33577.png | 25.6 KB | ||
Others | emd_33577_half_map_1.map.gz emd_33577_half_map_2.map.gz | 84.7 MB 84.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33577 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33577 | HTTPS FTP |
-Validation report
Summary document | emd_33577_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_33577_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_33577_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_33577_validation.cif.gz | 15.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33577 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33577 | HTTPS FTP |
-Related structure data
Related structure data | 7y20MC 7y1yC 7y1zC 7y21C 8i9eC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_33577.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_33577_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_33577_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : S-ECD (Omicron BA.3) in complex with 2 PD of ACE2
Entire | Name: S-ECD (Omicron BA.3) in complex with 2 PD of ACE2 |
---|---|
Components |
|
-Supramolecule #1: S-ECD (Omicron BA.3) in complex with 2 PD of ACE2
Supramolecule | Name: S-ECD (Omicron BA.3) in complex with 2 PD of ACE2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: S-ECD (Omicron BA.3)
Supramolecule | Name: S-ECD (Omicron BA.3) / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: PD of ACE2
Supramolecule | Name: PD of ACE2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
---|
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 140.531797 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR DLPQGFSALE PLVDLPIGIN ITRFQTLLAL HR SYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESI VRFPNI TNLCPFDEVF NATRFASVYA WNRKRISNCV ADYSVLYNFA PFFTFKCYGV SPTKLNDLCF TNVYADSFVI RGNE VRQIA PGQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKVSGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGF NCYF PLRSYGFRPT YGVGHQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFG RDI ADTTDAVRDP QTLEILDITP CSFGGVSVIT PGTNTSNQVA VLYQGVNCTE VPVAIHADQL TPTWRVYSTG SNVFQTR AG CLIGAEYVNN SYECDIPIGA GICASYQTQT KSHGSASSVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEI L PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLKRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKYF GGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQ IPFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNHN AQALNTLVKQ L SSKFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KG YHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNC DVVIGI VNNTVYDPLQ PELDSFKEEL DKYFKNHTSP DVDLGDISGI NASVVNIQKE IDRLNEVAKN LNESLIDLQE LGKY EQGSG YIPEAPRDGQ AYVRKDGEWV LLSTFLLEGS DEVDAGSHHH HHHHHHHGSV EDYKDDDDK UniProtKB: Spike glycoprotein |
-Macromolecule #2: Processed angiotensin-converting enzyme 2
Macromolecule | Name: Processed angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 72.039992 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGVKVLFALI CIAVAEAGTS TIEEQAKTFL DKFNHEAEDL FYQSSLASWN YNTNITEENV QNMNNAGDKW SAFLKEQSTL AQMYPLQEI QNLTVKLQLQ ALQQNGSSVL SEDKSKRLNT ILNTMSTIYS TGKVCNPDNP QECLLLEPGL NEIMANSLDY N ERLWAWES ...String: MGVKVLFALI CIAVAEAGTS TIEEQAKTFL DKFNHEAEDL FYQSSLASWN YNTNITEENV QNMNNAGDKW SAFLKEQSTL AQMYPLQEI QNLTVKLQLQ ALQQNGSSVL SEDKSKRLNT ILNTMSTIYS TGKVCNPDNP QECLLLEPGL NEIMANSLDY N ERLWAWES WRSEVGKQLR PLYEEYVVLK NEMARANHYE DYGDYWRGDY EVNGVDGYDY SRGQLIEDVE HTFEEIKPLY EH LHAYVRA KLMNAYPSYI SPIGCLPAHL LGDMWGRFWT NLYSLTVPFG QKPNIDVTDA MVDQAWDAQR IFKEAEKFFV SVG LPNMTQ GFWENSMLTD PGNVQKAVCH PTAWDLGKGD FRILMCTKVT MDDFLTAHHE MGHIQYDMAY AAQPFLLRNG ANEG FHEAV GEIMSLSAAT PKHLKSIGLL SPDFQEDNET EINFLLKQAL TIVGTLPFTY MLEKWRWMVF KGEIPKDQWM KKWWE MKRE IVGVVEPVPH DETYCDPASL FHVSNDYSFI RYYTRTLYQF QFQEALCQAA KHEGPLHKCD ISNSTEAGQK LFNMLR LGK SEPWTLALEN VVGAKNMNVR PLLNYFEPLF TWLKDQNKNS FVGWSTDWSP YADDYKDDDD K UniProtKB: Angiotensin-converting enzyme 2 |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 27 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0.6) / Number images used: 55521 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |