[English] 日本語
Yorodumi- EMDB-27318: CryoEM structure of Hantavirus ANDV Gn(H) protein complex with 2F... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27318 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | CryoEM structure of Hantavirus ANDV Gn(H) protein complex with 2Fabs ANDV-5 and ANDV-34 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Function / homology | Function and homology information symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / immunoglobulin complex, circulating / immunoglobulin receptor binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / complement activation, classical pathway / antigen binding / endocytosis involved in viral entry into host cell / antibacterial humoral response ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / immunoglobulin complex, circulating / immunoglobulin receptor binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / complement activation, classical pathway / antigen binding / endocytosis involved in viral entry into host cell / antibacterial humoral response / host cell surface / host cell endoplasmic reticulum membrane / blood microparticle / induction by virus of host autophagy / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / virion membrane / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Andes orthohantavirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Binshtein E / Crowe JE | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: Elife / Year: 2023 Title: Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies. Authors: Taylor B Engdahl / Elad Binshtein / Rebecca L Brocato / Natalia A Kuzmina / Lucia M Principe / Steven A Kwilas / Robert K Kim / Nathaniel S Chapman / Monique S Porter / Pablo Guardado-Calvo ...Authors: Taylor B Engdahl / Elad Binshtein / Rebecca L Brocato / Natalia A Kuzmina / Lucia M Principe / Steven A Kwilas / Robert K Kim / Nathaniel S Chapman / Monique S Porter / Pablo Guardado-Calvo / Félix A Rey / Laura S Handal / Summer M Diaz / Irene A Zagol-Ikapitte / Minh H Tran / W Hayes McDonald / Jens Meiler / Joseph X Reidy / Andrew Trivette / Alexander Bukreyev / Jay W Hooper / James E Crowe / Abstract: Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are ...Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_27318.map.gz | 20.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-27318-v30.xml emd-27318.xml | 23.3 KB 23.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27318_fsc.xml | 6.4 KB | Display | FSC data file |
Images | emd_27318.png | 68.8 KB | ||
Others | emd_27318_half_map_1.map.gz emd_27318_half_map_2.map.gz | 17 MB 17 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27318 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27318 | HTTPS FTP |
-Validation report
Summary document | emd_27318_validation.pdf.gz | 861.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_27318_full_validation.pdf.gz | 860.7 KB | Display | |
Data in XML | emd_27318_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_27318_validation.cif.gz | 16.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27318 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27318 | HTTPS FTP |
-Related structure data
Related structure data | 8dbzMC C: citing same article (ref.) M: atomic model generated by this map |
---|---|
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_27318.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.46 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_27318_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_27318_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Gn(H) in complex with Fabs ANDV-5 ANDV-34
Entire | Name: Gn(H) in complex with Fabs ANDV-5 ANDV-34 |
---|---|
Components |
|
-Supramolecule #1: Gn(H) in complex with Fabs ANDV-5 ANDV-34
Supramolecule | Name: Gn(H) in complex with Fabs ANDV-5 ANDV-34 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Glycoprotein N
Macromolecule | Name: Glycoprotein N / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Andes orthohantavirus |
Molecular weight | Theoretical: 38.767207 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TIYELKMECP HTVGLGQGYI IGSTELGLIS IEAASDIKLE SSCNFDLHTT SMAQKSFTQV EWRKKSDTTD TTNAASTTFE AQTKTVNLR GTCILAPELY DTLKKVKKTV LCYDLTCNQT HCQPTVYLIA PVLTCMSIRS CMASVFTSRI QVIYEKTHCV T GQLIEGQC ...String: TIYELKMECP HTVGLGQGYI IGSTELGLIS IEAASDIKLE SSCNFDLHTT SMAQKSFTQV EWRKKSDTTD TTNAASTTFE AQTKTVNLR GTCILAPELY DTLKKVKKTV LCYDLTCNQT HCQPTVYLIA PVLTCMSIRS CMASVFTSRI QVIYEKTHCV T GQLIEGQC FNPAHTLTLS QPAHTYDTVT LPISCFFTPK KSEQLKVIKT FEGILTKTGC TENALQGYYV CFLGSHSEPL IV PSLEDIR SAEVVSRMLV HPRGEDHDAI QNSQSHLRIV GPITAKVPST SSTDTLKGTA FAGVPMYSSL STLVRNADPE FVF SPGIVP ESNHSTCDKK TVPITWTGYL PISGEME |
-Macromolecule #2: Fv (H) ANDV-34
Macromolecule | Name: Fv (H) ANDV-34 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.609076 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVHLVQSGGE LRKPGSSVKV SCKASGGTFS SFAITWLRQA PGQGLEWVGA YIPVFGSAIH GQKVHGRVTL TADESTTTAY MELSSLRSE DTAVYFCARG PTQNWEYSYY TYFESWGQGT LVTVSS |
-Macromolecule #3: Fv (L) ANDV-34
Macromolecule | Name: Fv (L) ANDV-34 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.91224 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QIVLTQSPGT LSLSPGERAT LSCRASQSVT SRYLAWYQQK PGQAPRLLIY DTSSRATGIP DRFSGSGSET DFTLTISRLA PEDFAVYYC QQYGTSPAVT FGQGTRLEIK |
-Macromolecule #4: Fv (H) ANDV-5
Macromolecule | Name: Fv (H) ANDV-5 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 14.013572 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLLQSGAE VKKPGSSVRV SCQSSGDIYN YYGISWVRQA PGQGLEWMGG IIPVYGRPNY VQKFRGRVTF TVDKSTSTAY MELSTLRAD DTAVYYCARD TARSHYFGSG NDYGMDVWGQ GTTVIVSS |
-Macromolecule #5: Fv (L) ANDV-5
Macromolecule | Name: Fv (L) ANDV-5 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.187647 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPLS LPVTPGEPAS ISCRSSQSLL HSNGFNFVDW YLQKPGQSPQ LLIYLGSTRA SGVPDRFSGS GSGTDFTLEI SRVEAEDVG VYYCMQALQF PRTFGQGTKL DIK |
-Macromolecule #6: COV44-79 heavy chain constant domain
Macromolecule | Name: COV44-79 heavy chain constant domain / type: protein_or_peptide / ID: 6 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 10.58592 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKP SNTKVDKKVE PKSC |
-Macromolecule #7: Fab Fc (L) KappaC
Macromolecule | Name: Fab Fc (L) KappaC / type: protein_or_peptide / ID: 7 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.848126 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEV THQGLRSPVT KSFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS GLACIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 3110 / Average exposure time: 4.34 sec. / Average electron dose: 50.86 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
---|---|
Output model | PDB-8dbz: |