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Yorodumi- EMDB-23629: Cryo-EM structure of the HCMV pentamer bound by human neuropilin 2 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23629 | |||||||||
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Title | Cryo-EM structure of the HCMV pentamer bound by human neuropilin 2 | |||||||||
Map data | Focused refinement map, calculated in cryoSPARC and sharpened using DeepEMhancer. | |||||||||
Sample |
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Function / homology | Function and homology information vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus ...vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / branchiomotor neuron axon guidance / axon extension involved in axon guidance / NrCAM interactions / sympathetic neuron projection extension / Neurophilin interactions with VEGF and VEGFR / sympathetic ganglion development / neural crest cell migration involved in autonomic nervous system development / vascular endothelial growth factor receptor activity / nerve development / semaphorin receptor complex / outflow tract septum morphogenesis / semaphorin receptor activity / regulation of postsynapse organization / negative chemotaxis / cytokine binding / growth factor binding / semaphorin-plexin signaling pathway / positive regulation of endothelial cell proliferation / cellular response to leukemia inhibitory factor / positive regulation of endothelial cell migration / axon guidance / signaling receptor activity / heparin binding / postsynaptic membrane / angiogenesis / cell adhesion / axon / viral envelope / glutamatergic synapse / extracellular region / membrane / identical protein binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human betaherpesvirus 5 / Homo sapiens (human) / Human cytomegalovirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.65 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_23629.map.gz | 195.1 MB | EMDB map data format | |
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Header (meta data) | emd-23629-v30.xml emd-23629.xml | 26.5 KB 26.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23629_fsc.xml | 13.8 KB | Display | FSC data file |
Images | emd_23629.png | 99.7 KB | ||
Others | emd_23629_additional_1.map.gz emd_23629_half_map_1.map.gz emd_23629_half_map_2.map.gz | 187.2 MB 200.2 MB 200.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23629 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23629 | HTTPS FTP |
-Related structure data
Related structure data | 7m22MC 7kbaC 7kbbC 7lyvC 7lywC 7m1cC 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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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23629.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused refinement map, calculated in cryoSPARC and sharpened using DeepEMhancer. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.073 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Full map that was subsequently subjected to focused...
File | emd_23629_additional_1.map | ||||||||||||
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Annotation | Full map that was subsequently subjected to focused refinement. Calculated in cryoSPARC and sharpened using DeepEMhancer. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map B for focused refinement.
File | emd_23629_half_map_1.map | ||||||||||||
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Annotation | Half-map B for focused refinement. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map A for focused refinement.
File | emd_23629_half_map_2.map | ||||||||||||
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Annotation | Half-map A for focused refinement. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of ...
Entire | Name: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of human neuropilin 2 |
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Components |
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-Supramolecule #1: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of ...
Supramolecule | Name: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of human neuropilin 2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: The primary map is the result of a focused refinement that encompasses the HCMV UL proteins (UL128, UL130, UL131) and NRP2 domains a2b1b2. The included additional map is the non-focused ...Details: The primary map is the result of a focused refinement that encompasses the HCMV UL proteins (UL128, UL130, UL131) and NRP2 domains a2b1b2. The included additional map is the non-focused refinement in which the entire HCMV pentamer ectodomain and the entirety of NRP2 a1a2b1b2 can be observed. |
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Molecular weight | Experimental: 230 KDa |
-Supramolecule #2: The ectodomain of the HCMV pentamer
Supramolecule | Name: The ectodomain of the HCMV pentamer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Human betaherpesvirus 5 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: Domains a1a2b1b2 of human neuropilin 2
Supramolecule | Name: Domains a1a2b1b2 of human neuropilin 2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Envelope protein UL128
Macromolecule | Name: Envelope protein UL128 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human cytomegalovirus |
Molecular weight | Theoretical: 16.684299 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EECCEFINVN HPPERCYDFK MCNRFTVALR CPDGEVCYSP EKTAEIRGIV TTMTHSLTRQ VVHNKLTSCN YNPLYLEADG RIRCGKVND KAQYLLGAAG SVPYRWINLE YDKITRIVGL DQYLESVKKH KRLDVCRAKM GYMLQ |
-Macromolecule #2: Envelope glycoprotein UL130
Macromolecule | Name: Envelope glycoprotein UL130 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human cytomegalovirus |
Molecular weight | Theoretical: 21.761678 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SPWSTLTANQ NPSPPWSKLT YSKPHDAATF YCPFLYPSPP RSPLQFSGFQ QVSTGPECRN ETLYLLYNRE GQTLVERSST WVKKVIWYL SGRNQTILQR MPQTASKPSD GNVQISVEDA KIFGAHMVPK QTKLLRFVVN DGTRYQMCVM KLESWAHVFR D YSVSFQVR LTFTEANNQT YTFCTHPNLI V |
-Macromolecule #3: UL131A
Macromolecule | Name: UL131A / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human cytomegalovirus |
Molecular weight | Theoretical: 13.005457 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QCQRETAEKN DYYRVPHYWD ACSRALPDQT RYKYVEQLVD LTLNYHYDAS HGLDNFDVLK RINVTEVSLL ISDFRRQNRR GGTNKRTTF NAAGSLAPHA RSLEFSVRLF AN |
-Macromolecule #4: Neuropilin-2
Macromolecule | Name: Neuropilin-2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 65.430434 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QPDPPCGGRL NSKDAGYITS PGYPQDYPSH QNCEWIVYAP EPNQKIVLNF NPHFEIEKHD CKYDFIEIRD GDSESADLLG KHCGNIAPP TIISSGSMLY IKFTSDYARQ GAGFSLRYEI FKTGSEDCSK NFTSPNGTIE SPGFPEKYPH NLDCTFTILA K PKMEIILQ ...String: QPDPPCGGRL NSKDAGYITS PGYPQDYPSH QNCEWIVYAP EPNQKIVLNF NPHFEIEKHD CKYDFIEIRD GDSESADLLG KHCGNIAPP TIISSGSMLY IKFTSDYARQ GAGFSLRYEI FKTGSEDCSK NFTSPNGTIE SPGFPEKYPH NLDCTFTILA K PKMEIILQ FLIFDLEHDP LQVGEGDCKY DWLDIWDGIP HVGPLIGKYC GTKTPSELRS STGILSLTFH TDMAVAKDGF SA RYYLVHQ EPLENFQCNV PLGMESGRIA NEQISASSTY SDGRWTPQQS RLHGDDNGWT PNLDSNKEYL QVDLRFLTML TAI ATQGAI SRETQNGYYV KSYKLEVSTN GEDWMVYRHG KNHKVFQANN DATEVVLNKL HAPLLTRFVR IRPQTWHSGI ALRL ELFGC RVTDAPCSNM LGMLSGLIAD SQISASSTQE YLWSPSAARL VSSRSGWFPR IPQAQPGEEW LQVDLGTPKT VKGVI IQGA RGGDSITAVE ARAFVRKFKV SYSLNGKDWE YIQDPRTQQP KLFEGNMHYD TPDIRRFDPI PAQYVRVYPE RWSPAG IGM RLEVLGCDWT GSLEVLFQ |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #6: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 1 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.4 mg/mL | ||||||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY ARRAY / Pretreatment - Type: PLASMA CLEANING | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV Details: Grid was blotted with a force of -6 for 3 seconds. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Details | Collected from a single grid at -30 degrees tilt |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |