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Yorodumi- EMDB-22788: Cryo-EM structure of the HCMV pentamer bound by Fabs 2-18 and 8I21 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22788 | |||||||||
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Title | Cryo-EM structure of the HCMV pentamer bound by Fabs 2-18 and 8I21 | |||||||||
Map data | Locally refined map sharpened using DeepEMhancer | |||||||||
Sample |
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Function / homology | Herpesvirus UL130, cytomegalovirus / HCMV glycoprotein pUL130 / viral envelope / Envelope glycoprotein UL130 / UL128 / UL131A Function and homology information | |||||||||
Biological species | Human betaherpesvirus 5 / Homo sapiens (human) / Human cytomegalovirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.02 Å | |||||||||
Authors | Wrapp D / McLellan JS | |||||||||
Citation | Journal: Sci Adv / Year: 2022 Title: Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies. Authors: Daniel Wrapp / Xiaohua Ye / Zhiqiang Ku / Hang Su / Harrison G Jones / Nianshuang Wang / Akaash K Mishra / Daniel C Freed / Fengsheng Li / Aimin Tang / Leike Li / Dabbu Kumar Jaijyan / Hua ...Authors: Daniel Wrapp / Xiaohua Ye / Zhiqiang Ku / Hang Su / Harrison G Jones / Nianshuang Wang / Akaash K Mishra / Daniel C Freed / Fengsheng Li / Aimin Tang / Leike Li / Dabbu Kumar Jaijyan / Hua Zhu / Dai Wang / Tong-Ming Fu / Ningyan Zhang / Zhiqiang An / Jason S McLellan / Abstract: Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into ...Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22788.map.gz | 189.8 MB | EMDB map data format | |
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Header (meta data) | emd-22788-v30.xml emd-22788.xml | 30.3 KB 30.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22788_fsc.xml | 14.5 KB | Display | FSC data file |
Images | emd_22788.png | 54.2 KB | ||
Others | emd_22788_additional_1.map.gz emd_22788_additional_2.map.gz emd_22788_half_map_1.map.gz emd_22788_half_map_2.map.gz | 107.9 MB 190.6 MB 200.4 MB 200.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22788 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22788 | HTTPS FTP |
-Related structure data
Related structure data | 7kbbMC 7kbaC 7lyvC 7lywC 7m1cC 7m22C 7m30C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_22788.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Locally refined map sharpened using DeepEMhancer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.047 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Locally refined map unsharpened
File | emd_22788_additional_1.map | ||||||||||||
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Annotation | Locally refined map unsharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Full map sharpened with DeepEMhancer
File | emd_22788_additional_2.map | ||||||||||||
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Annotation | Full map sharpened with DeepEMhancer | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_22788_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_22788_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : HCMV pentamer bound by antibodies 2-18 and 8I21
+Supramolecule #1: HCMV pentamer bound by antibodies 2-18 and 8I21
+Supramolecule #2: HCMV pentamer (refinement focused on three of the subunits)
+Supramolecule #3: Fab 2-18
+Supramolecule #4: Fab 8I21
+Macromolecule #1: 2-18 Fab Heavy Chain
+Macromolecule #2: 2-18 Fab Light Chain
+Macromolecule #3: Envelope protein UL128
+Macromolecule #4: Envelope glycoprotein UL130
+Macromolecule #5: UL131A
+Macromolecule #6: 8I21 Fab Heavy Chain
+Macromolecule #7: 8I21 Fab Light Chain
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.25 mg/mL | |||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: PLASMA CLEANING | |||||||||||||||
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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 36.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |