[English] 日本語
Yorodumi- EMDB-32728: Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in comple... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32728 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | antibody / complex / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information 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 ...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 / 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 / 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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.08 Å | |||||||||
Authors | Du S / Xiao JY | |||||||||
Funding support | 1 items
| |||||||||
Citation | Journal: Cell Rep / Year: 2022 Title: Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents. Authors: Yunlong Cao / Fanchong Jian / Zhiying Zhang / Ayijiang Yisimayi / Xiaohua Hao / Linlin Bao / Fei Yuan / Yuanling Yu / Shuo Du / Jing Wang / Tianhe Xiao / Weiliang Song / Ying Zhang / Pulan ...Authors: Yunlong Cao / Fanchong Jian / Zhiying Zhang / Ayijiang Yisimayi / Xiaohua Hao / Linlin Bao / Fei Yuan / Yuanling Yu / Shuo Du / Jing Wang / Tianhe Xiao / Weiliang Song / Ying Zhang / Pulan Liu / Ran An / Peng Wang / Yao Wang / Sijie Yang / Xiao Niu / Yuhang Zhang / Qingqing Gu / Fei Shao / Yaling Hu / Weidong Yin / Aihua Zheng / Youchun Wang / Chuan Qin / Ronghua Jin / Junyu Xiao / Xiaoliang Sunney Xie / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_32728.map.gz | 167.9 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-32728-v30.xml emd-32728.xml | 12.3 KB 12.3 KB | Display Display | EMDB header |
Images | emd_32728.png | 25 KB | ||
Filedesc metadata | emd-32728.cif.gz | 5.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32728 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32728 | HTTPS FTP |
-Validation report
Summary document | emd_32728_validation.pdf.gz | 484.7 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_32728_full_validation.pdf.gz | 484.3 KB | Display | |
Data in XML | emd_32728_validation.xml.gz | 6.6 KB | Display | |
Data in CIF | emd_32728_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32728 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32728 | HTTPS FTP |
-Related structure data
Related structure data | 7wrjMC 7wryC 7y0cC 7y0vC 7y0wC 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_32728.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Sample components
-Entire : the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab
Entire | Name: the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab |
---|---|
Components |
|
-Supramolecule #1: the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab
Supramolecule | Name: the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 21.968818 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY ...String: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY GVGHQPYRVV VLSFELLHAP ATVCG UniProtKB: Spike glycoprotein |
-Macromolecule #2: BD55-4637H
Macromolecule | Name: BD55-4637H / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 27.750688 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGWSLILLFL VAVATRVLSQ ITLKESGPTL VKPKQTLTLT CTFSGFSLKK NGVGVGWIRQ PPGKALEWLA LIYWDDSKRY NPSLKTRLT ITGDTSKNQV VLTLTNVDPV DTATYFCAHR PDLDSDLIVV DAFDMWGQGT MVTVSSASTK GPSVFPLAPS S KSTSGGTA ...String: MGWSLILLFL VAVATRVLSQ ITLKESGPTL VKPKQTLTLT CTFSGFSLKK NGVGVGWIRQ PPGKALEWLA LIYWDDSKRY NPSLKTRLT ITGDTSKNQV VLTLTNVDPV DTATYFCAHR PDLDSDLIVV DAFDMWGQGT MVTVSSASTK GPSVFPLAPS S KSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VD KKVEPKS CDKTHHHHHH |
-Macromolecule #3: BD55-4637L
Macromolecule | Name: BD55-4637L / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.855613 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGWSCIILFL VATATGVHSQ SVLTQPPSAS GTPGQRVTIS CSGSSSNIGR NTVNWYQHLP GTVPKLLIYH NNHRPSGVPG RFSGSKSGT SASLAISGLQ SEDEADYYCE TWDDSLSGVV FGAGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI S DFYPGAVT ...String: MGWSCIILFL VATATGVHSQ SVLTQPPSAS GTPGQRVTIS CSGSSSNIGR NTVNWYQHLP GTVPKLLIYH NNHRPSGVPG RFSGSKSGT SASLAISGLQ SEDEADYYCE TWDDSLSGVV FGAGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI S DFYPGAVT VAWKADSSPV KAGVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
---|---|
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: 58.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.08 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 192163 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |