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- EMDB-46920: HCMV gH/UL116/UL141 3-mer complex, ectodomain -

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Basic information

Entry
Database: EMDB / ID: EMD-46920
TitleHCMV gH/UL116/UL141 3-mer complex, ectodomain
Map data
Sample
  • Complex: HCMV gH/UL116/UL141 3-mer complex
    • Protein or peptide: Envelope glycoprotein H
    • Protein or peptide: Protein UL141
    • Protein or peptide: UL116
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsSurface protein complex / VIRAL PROTEIN
Function / homology
Function and homology information


symbiont-mediated perturbation of host natural killer cell mediated immune response / host cell endosome / host cell endoplasmic reticulum membrane / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
Herpesvirus membrane glycoprotein UL141 / UL141-like superfamily / Herpes-like virus membrane glycoprotein UL141 / Herpesvirus glycoprotein H main domain / Herpesvirus glycoprotein H / Herpesvirus glycoprotein H, C-terminal / Herpesvirus glycoprotein H, C-terminal domain superfamily / Herpesvirus glycoprotein H C-terminal domain / Immunoglobulin-like domain superfamily
Similarity search - Domain/homology
Envelope glycoprotein H / UL116 / Protein UL141
Similarity search - Component
Biological speciesHuman betaherpesvirus 5
Methodsingle particle reconstruction / cryo EM / Resolution: 3.51 Å
AuthorsNorris MJ / Benedict CA / Kamil JP / Saphire EO
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: bioRxiv / Year: 2024
Title: A noncanonical glycoprotein H complex enhances cytomegalovirus entry.
Authors: Michael J Norris / Lauren A Henderson / Mohammed N A Siddiquey / Jieyun Yin / Kwangsun Yoo / Simon Brunel / Erica Ollmann Saphire / Chris A Benedict / Jeremy P Kamil /
Abstract: Human cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the ...Human cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the incomplete understanding of the diverse protein complexes the virus uses to infect cells. In , the gH/gL glycoprotein heterodimer is expected to be a basal element of virion cell entry machinery. For HCMV, gH/gL forms a "trimer" with gO and a "pentamer" with UL128, UL130, and UL131A, with each complex binding distinct receptors to enter varied cell types. Here, we reveal a third glycoprotein complex, abundant in HCMV virions, which significantly enhances infection of endothelial cells. In this "3-mer" complex, gH, without gL, associates with UL116 and UL141, an immunoevasin previously known to function in an intracellular role. Cryo-EM reveals the virion-surface 3-mer is structurally unique among gH complexes, with gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. Given that antibodies directed at gH and UL141 each can restrict HCMV replication, our work highlights this virion surface complex as a new target for vaccines and antiviral therapies.
History
DepositionSep 6, 2024-
Header (metadata) releaseNov 20, 2024-
Map releaseNov 20, 2024-
UpdateNov 20, 2024-
Current statusNov 20, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46920.png

Downloads & links

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Map

FileDownload / File: emd_46920.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.32 Å/pix.
x 256 pix.
= 337.92 Å		1.32 Å/pix.
x 256 pix.
= 337.92 Å		1.32 Å/pix.
x 256 pix.
= 337.92 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.32 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.11
Minimum - Maximum-0.32355607 - 0.6855886
Average (Standard dev.)-0.00026637551 (±0.015753835)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 337.92 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_46920_msk_1.map
Projections & Slices
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Histogram

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Half map: #2

Fileemd_46920_half_map_1.map
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Half map: #1

Fileemd_46920_half_map_2.map
Projections & Slices
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Sample components

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Entire : HCMV gH/UL116/UL141 3-mer complex

EntireName: HCMV gH/UL116/UL141 3-mer complex
Components
  • Complex: HCMV gH/UL116/UL141 3-mer complex
    • Protein or peptide: Envelope glycoprotein H
    • Protein or peptide: Protein UL141
    • Protein or peptide: UL116
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: HCMV gH/UL116/UL141 3-mer complex

SupramoleculeName: HCMV gH/UL116/UL141 3-mer complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Human betaherpesvirus 5

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Macromolecule #1: Envelope glycoprotein H

MacromoleculeName: Envelope glycoprotein H / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Human betaherpesvirus 5 / Strain: TB40-BAC4
Molecular weightTheoretical: 77.497164 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ASEALDPHAF HLLLNTYGRP IRFLRENTTQ CTYNSSLRNS TVVRENAISF NFFQSYNQYY VFHMPRCLFA GPLAEQFLNQ VDLTETLER YQQRLNTYAL VSKDLASYRS FSQQLKAQDS LGQQPTTVPP PIDLSIPHVW MPPQTTPHDW KGSHTTSGLH R PHFNQTCI ...String:
ASEALDPHAF HLLLNTYGRP IRFLRENTTQ CTYNSSLRNS TVVRENAISF NFFQSYNQYY VFHMPRCLFA GPLAEQFLNQ VDLTETLER YQQRLNTYAL VSKDLASYRS FSQQLKAQDS LGQQPTTVPP PIDLSIPHVW MPPQTTPHDW KGSHTTSGLH R PHFNQTCI LFDGHDLLFS TVTPCLHQGF YLMDELRYVK ITLTEDFFVV TVSIDDDTPM LLIFGHLPRV LFKAPYQRDN FI LRQTEKH ELLVLVKKTQ LNRHSYLKDS DFLDAALDFN YLDLSALLRN SFHRYAVDVL KSGRCQMLDR RTVEMAFAYA LAL FAAARQ EEAGTEISIP RALDRQAALL QIQEFMITCL SQTPPRTTLL LYPTAVDLAK RALWTPDQIT DITSLVRLVY ILSK QNQQH LIPQWALRQI ADFALQLHKT HLASFLSAFA RQELYLMGSL VHSMLVHTTE RREIFIVETG LCSLAELSHF TQLLA HPHH EYLSDLYTPC SSSGRRDHSL ERLTRLFPDA TVPATVPAAL SILSTMQPST LETFPDLFCL PLGESFSALT VSEHVS YVV TNQYLIKGIS YPVSTTVVGQ SLIITQTDSQ SKCELTRNMH TTHSITAALN ISLENCAFCQ SALLEYDDTQ GVINIMY MH DSDDVLFALD PYNEVVVSSP RTHYLMLLKN GTVLEVTD

UniProtKB: Envelope glycoprotein H

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Macromolecule #2: Protein UL141

MacromoleculeName: Protein UL141 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Human betaherpesvirus 5 / Strain: Merlin
Molecular weightTheoretical: 31.039045 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SFPFATADIA EKMWAENYET TSPAPVLVAE GEQVTIPCTV MTHSWPMVSI RARFCRSHDG SDELILDAVK GHRLMNGLQY RLPYATWNF SQLHLGQIFS LTFNVSTDTA GMYECVLRNY SHGLIMQRFV ILTQLETLSR PDEPCCTPAL GRYSLGDQIW S PTPWRLRN ...String:
SFPFATADIA EKMWAENYET TSPAPVLVAE GEQVTIPCTV MTHSWPMVSI RARFCRSHDG SDELILDAVK GHRLMNGLQY RLPYATWNF SQLHLGQIFS LTFNVSTDTA GMYECVLRNY SHGLIMQRFV ILTQLETLSR PDEPCCTPAL GRYSLGDQIW S PTPWRLRN HDCGMYRGFQ RNYFYIGRAD AEDCWKPACP DEEPDRCWTV IQRYRLPGDC YRSQPHPPKF LPVTPAPPAD ID TGMSPWA TRGGSGGGSL EVLFQGPGHH HHHHHH

UniProtKB: Protein UL141

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Macromolecule #3: UL116

MacromoleculeName: UL116 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Human betaherpesvirus 5 / Strain: TB40-BAC4
Molecular weightTheoretical: 35.321906 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: VETNATTVTS TTAAAATTNT TVATTGTTTT SPNVTSTTSN TVITPTTVSS VSNLTSSATS IPISTSTVSG TRNTRNNNTT TIGTNVTSP SPSVSILTTV TPAATSTTSN NGDVTSDYTP TFDLENITTT RAPTRPPAQD LCSHNLSIIL YEEESQSSVD I AVDEEEPE ...String:
VETNATTVTS TTAAAATTNT TVATTGTTTT SPNVTSTTSN TVITPTTVSS VSNLTSSATS IPISTSTVSG TRNTRNNNTT TIGTNVTSP SPSVSILTTV TPAATSTTSN NGDVTSDYTP TFDLENITTT RAPTRPPAQD LCSHNLSIIL YEEESQSSVD I AVDEEEPE LEDDDEYDEL WFPLYFEAEC NLNYTLQYVN HSCDYSVRQS SVSFPPWRDI DSVTFVPRNL SNCSAHGLAV IV AGNQTWY VNPFSLAHLL DAIYNVLGIE DLSANFRRQL APYRHTLIVP QTGGSGGSGS DDDDKAGWSH PQFEKGGGSG GGS GGGSWS HPQFEK

UniProtKB: UL116

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.8 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 119525
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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