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Yorodumi- EMDB-32732: Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32732 | |||||||||
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Title | Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex | |||||||||
Map data | ||||||||||
Sample |
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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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | SARS coronavirus B012 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
Authors | Zhang ZZ / Xiao JJ | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2022 Title: BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan ...Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan Liu / Ran An / Xiaohua Hao / Yao Wang / Jing Wang / Rui Feng / Haiyan Sun / Lijuan Zhao / Wen Zhang / Dong Zhao / Jiang Zheng / Lingling Yu / Can Li / Na Zhang / Rui Wang / Xiao Niu / Sijie Yang / Xuetao Song / Yangyang Chai / Ye Hu / Yansong Shi / Linlin Zheng / Zhiqiang Li / Qingqing Gu / Fei Shao / Weijin Huang / Ronghua Jin / Zhongyang Shen / Youchun Wang / Xiangxi Wang / Junyu Xiao / Xiaoliang Sunney Xie / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune- ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles, epitope distribution and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab and cilgavimab can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32732.map.gz | 168.2 MB | EMDB map data format | |
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Header (meta data) | emd-32732-v30.xml emd-32732.xml | 13.3 KB 13.3 KB | Display Display | EMDB header |
Images | emd_32732.png | 57 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32732 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32732 | HTTPS FTP |
-Related structure data
Related structure data | 7wrlMC 7wr8C 7wroC 7wrzC 7x6aC 7xiwC 7xixC 7xiyC 7xizC 7xnqC 7xnrC 7xnsC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32732.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex
Entire | Name: Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex |
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Components |
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-Supramolecule #1: Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex
Supramolecule | Name: Local structure of BD55-1239 Fab and SARS-COV2 Omicron RBD complex type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: SARS coronavirus B012 |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: BD55-1239H
Macromolecule | Name: BD55-1239H / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: SARS coronavirus B012 |
Molecular weight | Theoretical: 13.828252 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGDIYS TYASSWVRQA PGQGLEWMGR IIPVSGTVNY ADNFQGRVTI TADKSTSTAY MELRSLTSE DTAVYYCARD VARGGYSGTD FFDYYYGMDV WGQGTTVT |
-Macromolecule #2: BD55-1239L
Macromolecule | Name: BD55-1239L / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: SARS coronavirus B012 |
Molecular weight | Theoretical: 11.049867 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SALTQPASVS GSPGQSITIS CTGTSSDVGG YNYVSWYQQH PDKAPKLLIY DVNNRPSGVS TRFSGSKSGN TASLTISRLQ TDDEADYSC SSYTSSNTWV FGGGTK |
-Macromolecule #3: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: SARS coronavirus B012 |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: OTHER |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.07 e/Å2 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: OTHER |
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Final angle assignment | Type: OTHER |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.51 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 3300 |