[English] 日本語
Yorodumi- EMDB-27703: Structure of RBD directed antibody DH1047 in complex with SARS-Co... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27703 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of RBD directed antibody DH1047 in complex with SARS-CoV-2 spike: Local refinement of RBD-Fab interace | |||||||||
Map data | Structure of RBD directed antibody DH1047 in complex with SARS-CoV-2 spike: Local refinement of RBD-Fab interace | |||||||||
Sample |
| |||||||||
Keywords | RBD / Fab / Viral Protein / Viral Protein-Immune System Complex | |||||||||
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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.77 Å | |||||||||
Authors | May AJ / Manne K / Acharya P | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: bioRxiv / Year: 2023 Title: Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates. Authors: R Dilshan Malewana / Victoria Stalls / Aaron May / Xiaozhi Lu / David R Martinez / Alexandra Schäfer / Dapeng Li / Maggie Barr / Laura L Sutherland / Esther Lee / Robert Parks / Whitney ...Authors: R Dilshan Malewana / Victoria Stalls / Aaron May / Xiaozhi Lu / David R Martinez / Alexandra Schäfer / Dapeng Li / Maggie Barr / Laura L Sutherland / Esther Lee / Robert Parks / Whitney Edwards Beck / Amanda Newman / Kevin W Bock / Mahnaz Minai / Bianca M Nagata / C Todd DeMarco / Thomas N Denny / Thomas H Oguin / Wes Rountree / Yunfei Wang / Katayoun Mansouri / Robert J Edwards / Gregory D Sempowski / Amanda Eaton / Hiromi Muramatsu / Rory Henderson / Ying Tam / Christopher Barbosa / Juanjie Tang / Derek W Cain / Sampa Santra / Ian N Moore / Hanne Andersen / Mark G Lewis / Hana Golding / Robert Seder / Surender Khurana / David C Montefiori / Norbert Pardi / Drew Weissman / Ralph S Baric / Priyamvada Acharya / Barton F Haynes / Kevin O Saunders / Abstract: Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute ...Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOCs including Omicron XBB.1.5, but lacked cross-Sarbecovirus neutralization. Structural analysis showed that the macaque broad SARS-CoV-2 VOC nAbs bound to the same epitope as a human broad SARS-CoV-2 VOC nAb, DH1193. Vaccine-induced antibodies that targeted the RBD inner face neutralized multiple Sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike lacking proline substitutions encoded by nucleoside-modified mRNA can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human Sarbecoviruses or recent Omicron VOCs. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_27703.map.gz | 117.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-27703-v30.xml emd-27703.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27703_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_27703.png | 41.1 KB | ||
Filedesc metadata | emd-27703.cif.gz | 6.1 KB | ||
Others | emd_27703_half_map_1.map.gz emd_27703_half_map_2.map.gz | 115.8 MB 115.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27703 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27703 | HTTPS FTP |
-Related structure data
Related structure data | 8dtkMC 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_27703.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Structure of RBD directed antibody DH1047 in complex with SARS-CoV-2 spike: Local refinement of RBD-Fab interace | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.058 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half Map 1
File | emd_27703_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 2
File | emd_27703_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : RBD directed antibody DH1047 in complex with SARS-CoV-2 Spike
Entire | Name: RBD directed antibody DH1047 in complex with SARS-CoV-2 Spike |
---|---|
Components |
|
-Supramolecule #1: RBD directed antibody DH1047 in complex with SARS-CoV-2 Spike
Supramolecule | Name: RBD directed antibody DH1047 in complex with SARS-CoV-2 Spike type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: 22.758518 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: PNITNLCPFG EVFNATRFAS VYAWNRKRIS NCVADYSVLY NSASFSTFKC YGVSPTKLND LCFTNVYADS FVIRGDEVRQ IAPGQTGKI ADYNYKLPDD FTGCVIAWNS NNLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGST PCNGVEGFNC Y FPLQSYGF ...String: PNITNLCPFG EVFNATRFAS VYAWNRKRIS NCVADYSVLY NSASFSTFKC YGVSPTKLND LCFTNVYADS FVIRGDEVRQ IAPGQTGKI ADYNYKLPDD FTGCVIAWNS NNLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGST PCNGVEGFNC Y FPLQSYGF QPTNGVGYQP YRVVVLSFEL LHAPATVCGP KKSTN UniProtKB: Spike glycoprotein |
-Macromolecule #2: DH1047 Fab Light Chain
Macromolecule | Name: DH1047 Fab Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.638008 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPDS LAVSLGERAT INCRSSQSVL YSSNNENYLA WYQQKPGQPP KLLIYWASTR ESGIPDRFSG SGSGTDFTLT ISRLQAEDV AVYYCQQYYS LPRTFGQGTK VEIK |
-Macromolecule #3: DH1047 Fab Heavy Chain
Macromolecule | Name: DH1047 Fab Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 14.615087 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGASVQV SCQASANTFT NHYIHWVRQA PGQGLEWMGI IYPTGGNTIY AQGFQGRVTM TRDTSLNTIY LELSSLRSE DTAVYYCARD VRVDDSWSGY DLLSGGTYFD YWGQGTLVTV SSAS |
-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: 2 / 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: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 66.77 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |