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Open data
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Basic information
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Title | Local Cryo-EM structure of HCMV gH/UL116 interaction | |||||||||
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![]() | Surface protein complex / VIRAL PROTEIN | |||||||||
Function / homology | ![]() symbiont-mediated perturbation of host natural killer cell mediated immune response / host cell endosome / host cell endoplasmic reticulum membrane / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.36 Å | |||||||||
![]() | Norris MJ / Benedict CA / Kamil JP / Saphire EO | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 7.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.7 KB 19.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.4 KB | Display | ![]() |
Images | ![]() | 87.3 KB | ||
Masks | ![]() | 15.6 MB | ![]() | |
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() | 14.5 MB 14.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9diyMC ![]() 9dixC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #1
File | emd_46921_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_46921_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : local structure of gH/UL116 interaction
Entire | Name: local structure of gH/UL116 interaction |
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Components |
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-Supramolecule #1: local structure of gH/UL116 interaction
Supramolecule | Name: local structure of gH/UL116 interaction / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Envelope glycoprotein H
Macromolecule | Name: Envelope glycoprotein H / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 77.497164 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #2: UL116
Macromolecule | Name: UL116 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 35.321906 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #3: Protein UL141
Macromolecule | Name: Protein UL141 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 31.039045 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 9 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.8 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |