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Open data
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Basic information
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| Title | HCoV-HKU1 C S 2P in complex with H501-008 Fab (global cryoEM) | |||||||||
Map data | HCov-HKU1 C S 2P in complex with H501-008 Fab | |||||||||
Sample |
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Keywords | coronavirus / HKU1 / mAb / cryoEM / VIRAL PROTEIN | |||||||||
| Biological species | Human coronavirus HKU1 / Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Vasquez S / Barnes CO | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2025Title: Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site. Authors: Lingshu Wang / Jeswin Joseph / Sheena Vasquez / Daniel Wrapp / Timothy P Sheahan / Christian K O Dzuvor / Osnat Rosen / Robert N Kirchdoerfer / Olubukola M Abiona / Catherine Hammond / Wei ...Authors: Lingshu Wang / Jeswin Joseph / Sheena Vasquez / Daniel Wrapp / Timothy P Sheahan / Christian K O Dzuvor / Osnat Rosen / Robert N Kirchdoerfer / Olubukola M Abiona / Catherine Hammond / Wei Shi / Sydney P Moak / Wing-Pui Kong / Yi Zhang / Michael R Eso / Ariane J Brown / Andrew B Ward / Ralph Baric / Jason S McLellan / Theodore C Pierson / John Mascola / Barney S Graham / Hadi M Yassine / Christopher O Barnes / Kizzmekia S Corbett-Helaire / ![]() Abstract: Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ~30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, ...Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ~30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, little is known about HCoV-HKU1's antigenic landscape. Thus, we characterized key interactions between HCoV-HKU1 spike (S) with monoclonal antibodies (mAbs) isolated from pre-pandemic HCoV-HKU1 convalescent PBMCs. We isolated 14 mAbs, which bound distinct S regions: receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Structural and functional studies revealed three groups of RBD-specific mAbs targeting diverse footprints within and around the TMPRSS2 receptor binding site, exemplified by: (1) The most potently neutralizing mAb, H501-022 (IC = 0.01 μg/mL), which recognizes the TMPRSS2 binding motif, thereby blocking receptor engagement; (2) mAb H501-008 (IC = 0.05 μg/mL) that binds a conserved, cross-reactive epitope outside of the TMPRSS2 binding site that is shared with HCoV-OC43; and (3) H501-018 (IC = 0.28 μg/mL) that recognizes both "up" and "down" RBD conformations at a distinct, non-overlapping site outside of the TMPRSS2 binding motif, distinguishing itself from H501-022 and H501-008, which bind exclusively to the "up" RBD conformation. These mAbs represent the first type-specific HCoV-HKU1 mAbs isolated from a convalescent donor. Our findings provide molecular insight into HCoV-HKU1 antibody recognition and neutralization mechanisms, importantly highlighting antigenic differences comparing HCoVs and pandemic CoVs - a critical step towards advancing universal CoV vaccine design. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_72934.map.gz | 450.8 MB | EMDB map data format | |
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| Header (meta data) | emd-72934-v30.xml emd-72934.xml | 19.8 KB 19.8 KB | Display Display | EMDB header |
| Images | emd_72934.png | 55.2 KB | ||
| Filedesc metadata | emd-72934.cif.gz | 4.8 KB | ||
| Others | emd_72934_additional_1.map.gz emd_72934_half_map_1.map.gz emd_72934_half_map_2.map.gz | 236.3 MB 442.8 MB 442.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-72934 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-72934 | 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_72934.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | HCov-HKU1 C S 2P in complex with H501-008 Fab | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.92 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: HCov-HKU1 C S 2P in complex with H501-008 Fab
| File | emd_72934_additional_1.map | ||||||||||||
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| Annotation | HCov-HKU1 C S 2P in complex with H501-008 Fab | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Half map: HCov-HKU1 C S 2P in complex with H501-008 Fab half map B
| File | emd_72934_half_map_1.map | ||||||||||||
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| Annotation | HCov-HKU1 C S 2P in complex with H501-008 Fab half map B | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Half map: HCov-HKU1 C S 2P in complex with H501-008 Fab half map A
| File | emd_72934_half_map_2.map | ||||||||||||
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| Annotation | HCov-HKU1 C S 2P in complex with H501-008 Fab half map A | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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Sample components
-Entire : HCoV-HKU1 C S 2P in complex with H501-008 Fab
| Entire | Name: HCoV-HKU1 C S 2P in complex with H501-008 Fab |
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| Components |
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-Supramolecule #1: HCoV-HKU1 C S 2P in complex with H501-008 Fab
| Supramolecule | Name: HCoV-HKU1 C S 2P in complex with H501-008 Fab / type: complex / ID: 1 / Parent: 0 |
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-Supramolecule #2: HCoV-HKU1 C S 2P
| Supramolecule | Name: HCoV-HKU1 C S 2P / type: complex / ID: 2 / Parent: 1 |
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| Source (natural) | Organism: Human coronavirus HKU1 / Strain: isolate N5 |
-Supramolecule #3: H501-008 Fab
| Supramolecule | Name: H501-008 Fab / type: complex / ID: 3 / Parent: 1 |
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| Source (natural) | Organism: Homo sapiens (human) |
-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 | 7 mg/mL | |||||||||
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| Buffer | pH: 8 Component:
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| Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa | |||||||||
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 2938 / Average exposure time: 3.4 sec. / Average electron dose: 40.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 150000 |
| Sample stage | Cooling holder cryogen: NITROGEN |
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About Yorodumi




Keywords
Human coronavirus HKU1
Homo sapiens (human)
Authors
United States, 1 items
Citation






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Processing
FIELD EMISSION GUN