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Yorodumi- EMDB-49520: Focused refinement of the prefusion F glycoprotein ectodomain of ... -
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| Title | Focused refinement of the prefusion F glycoprotein ectodomain of Nipah virus in complex with DS90 nanobody | |||||||||
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Keywords | F ectodomain / prefusion / viral protein / nipah virus | |||||||||
| Biological species | Henipavirus nipahense | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.59 Å | |||||||||
Authors | Low YS / Isaacs A / Modhiran N / Watterson D | |||||||||
| Funding support | Australia, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: A nanobody-based therapeutic targeting Nipah virus limits viral escape. Authors: Ariel Isaacs / Guillermo Valenzuela Nieto / Xinghai Zhang / Naphak Modhiran / Jennifer Barr / Nazia Thakur / Yu Shang Low / Rhys H Parry / James B Barnes / Ronald Jara / Johanna Himelreichs ...Authors: Ariel Isaacs / Guillermo Valenzuela Nieto / Xinghai Zhang / Naphak Modhiran / Jennifer Barr / Nazia Thakur / Yu Shang Low / Rhys H Parry / James B Barnes / Ronald Jara / Johanna Himelreichs / Yanfeng Yao / Camila Deride / Barbara Barthou-Gatica / Constanza Salinas-Rebolledo / Pamela Ehrenfeld / Jun Jet Hen / Noah Hayes / Devina Paramitha / Mahali S Morgan / Christopher L D McMillan / Martina L Jones / Trent P Munro / Alexander A Khromykh / Patrick C Reading / Paul R Young / Keith J Chappell / Yi Shi / Dalan Bailey / Glenn A Marsh / Sandra Chiu / Alejandro Rojas-Fernandez / Daniel Watterson / ![]() Abstract: Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an ...Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion glycoprotein nanobody with an anti-receptor-binding glycoprotein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within the fusion glycoprotein of NiV and HeV and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP monoclonal antibody m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_49520.map.gz | 323.9 MB | EMDB map data format | |
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| Header (meta data) | emd-49520-v30.xml emd-49520.xml | 20.2 KB 20.2 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_49520_fsc.xml | 14.9 KB | Display | FSC data file |
| Images | emd_49520.png | 54.8 KB | ||
| Masks | emd_49520_msk_1.map | 343 MB | Mask map | |
| Filedesc metadata | emd-49520.cif.gz | 5.8 KB | ||
| Others | emd_49520_half_map_1.map.gz emd_49520_half_map_2.map.gz | 318.1 MB 318.1 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-49520 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-49520 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_49520.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.8 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_49520_msk_1.map | ||||||||||||
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-Half map: #1
| File | emd_49520_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_49520_half_map_2.map | ||||||||||||
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Sample components
-Entire : Prefusion F glycoprotein ectodomain of Nipah virus ectodomain in ...
| Entire | Name: Prefusion F glycoprotein ectodomain of Nipah virus ectodomain in complex with DS90 nanobody |
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| Components |
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-Supramolecule #1: Prefusion F glycoprotein ectodomain of Nipah virus ectodomain in ...
| Supramolecule | Name: Prefusion F glycoprotein ectodomain of Nipah virus ectodomain in complex with DS90 nanobody type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Henipavirus nipahense |
| Molecular weight | Theoretical: 200 KDa |
-Macromolecule #1: Fusion glycoprotein from Nipah virus
| Macromolecule | Name: Fusion glycoprotein from Nipah virus / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Henipavirus nipahense |
| Recombinant expression | Organism: ![]() |
| Sequence | String: ILHYEKLSKI GLVKGVTRKY KIKSNPLTKD IVIKMIPNVS NMSQCTGSVM ENYKTRLNGI LTPIKGALEI YKNNTHDLVG DVRLAGVIM AGVAIGIATA AQITAGVALY EAMKNADNIN KLKSSIESTN EAVVKLQETA EKTVYVLTAL QDYINTNLVP T IDKISCKQ ...String: ILHYEKLSKI GLVKGVTRKY KIKSNPLTKD IVIKMIPNVS NMSQCTGSVM ENYKTRLNGI LTPIKGALEI YKNNTHDLVG DVRLAGVIM AGVAIGIATA AQITAGVALY EAMKNADNIN KLKSSIESTN EAVVKLQETA EKTVYVLTAL QDYINTNLVP T IDKISCKQ TELSLDLALS KYLSDLLFVF GPNLQDPVSN SMTIQAISQA FGGNYETLLR TLGYATEDFD DLLESDSITG QI IYVDLSS YYIIVRVYFP ILTEIQQAYI QELLPVSFNN DNSEWISIVP NFILVRNTLI SNIEIGFCLI TKRSVICNQD YAT PMTNNM RECLTGSTEK CPRELVVSSH VPRFALSNGV LFANCISVTC QCQTTGRAIS QSGEQTLLMI DNTTCPTAVL GNVI ISLGK YLGSVNYNSE GIAIGPPVFT DKVDISSQIS SMNQSLQQSK DYIKEAQRLL DT |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 0.04 mg/mL |
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| Buffer | pH: 7.4 |
| Vitrification | Cryogen name: ETHANE / Instrument: LEICA EM GP |
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Electron microscopy
| Microscope | JEOL CRYO ARM 300 |
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| Specialist optics | Energy filter - Name: In-column Omega Filter / Energy filter - Slit width: 20 eV |
| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 87.5 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | C2 aperture diameter: 40.0 µm / Calibrated magnification: 60000 / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 25.0 µm / Nominal defocus min: 5.0 µm / Nominal magnification: 60000 |
| Sample stage | Specimen holder model: JEOL CRYOSPECPORTER / Cooling holder cryogen: NITROGEN |
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Image processing
-Atomic model buiding 1
| Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 99.7 / Target criteria: Molprobity |
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About Yorodumi



Keywords
Henipavirus nipahense
Authors
Australia, 1 items
Citation



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FIELD EMISSION GUN
