+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38618 | |||||||||
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Title | SARS-CoV-2 RBD + IMCAS-364 + hACE2 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SARS-CoV-2 / broadly neutralizing antibodies / VIRAL PROTEIN/HYDROLASE/IMMUNE SYSTEM / VIRAL PROTEIN-HYDROLASE-IMMUNE SYSTEM 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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.16 Å | |||||||||
Authors | Tong Z / Cui Y / Xie Y / Tong J / Gao GF / Qi J | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Rep / Year: 2024 Title: Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1. Authors: Zhou Tong / Jianyu Tong / Wenwen Lei / Yufeng Xie / Yingzi Cui / Guowen Jia / Shihua Li / Zezhong Zhang / Zhimin Cheng / Xiao Xing / Haiyun Ma / Lan Deng / Rong Zhang / Xin Zhao / Kefang Liu ...Authors: Zhou Tong / Jianyu Tong / Wenwen Lei / Yufeng Xie / Yingzi Cui / Guowen Jia / Shihua Li / Zezhong Zhang / Zhimin Cheng / Xiao Xing / Haiyun Ma / Lan Deng / Rong Zhang / Xin Zhao / Kefang Liu / Qihui Wang / Jianxun Qi / Haomin Huang / Rui Song / Zhaoming Su / Guizhen Wu / Jing Lou / George Fu Gao / Abstract: The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic ...The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38618.map.gz | 157.2 MB | EMDB map data format | |
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Header (meta data) | emd-38618-v30.xml emd-38618.xml | 21 KB 21 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_38618_fsc.xml | 11.8 KB | Display | FSC data file |
Images | emd_38618.png | 65.8 KB | ||
Filedesc metadata | emd-38618.cif.gz | 7 KB | ||
Others | emd_38618_half_map_1.map.gz emd_38618_half_map_2.map.gz | 165.3 MB 165.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38618 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38618 | HTTPS FTP |
-Validation report
Summary document | emd_38618_validation.pdf.gz | 639.1 KB | Display | EMDB validaton report |
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Full document | emd_38618_full_validation.pdf.gz | 638.7 KB | Display | |
Data in XML | emd_38618_validation.xml.gz | 20.4 KB | Display | |
Data in CIF | emd_38618_validation.cif.gz | 26.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38618 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38618 | HTTPS FTP |
-Related structure data
Related structure data | 8xsfMC 8xseC 8xsiC 8xsjC 8xslC 8y0yC 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_38618.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: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_38618_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_38618_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Cryo-EM structure of SARS-CoV-2 RBD + IMCAS-364 + hACE2 (Global R...
+Supramolecule #1: Cryo-EM structure of SARS-CoV-2 RBD + IMCAS-364 + hACE2 (Global R...
+Supramolecule #2: ACE2
+Supramolecule #3: SARS-CoV-2 RBD
+Supramolecule #4: IMCAS-364
+Macromolecule #1: Angiotensin-converting enzyme 2
+Macromolecule #2: Spike protein S1
+Macromolecule #3: IMCAS-364 H chain
+Macromolecule #4: IMCAS-364 L chain
+Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #6: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 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: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |