[English] 日本語
Yorodumi- EMDB-73789: Cryo-EM structure of KSHV glycoprotein gHgL in complex with MLKH3... -
+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of KSHV glycoprotein gHgL in complex with MLKH3 and MLKH10 FABs | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | KSHV / glycoprotein / Antibody / IMMUNE SYSTEM | |||||||||
| Function / homology | Function and homology informationhost cell endosome membrane / host cell Golgi apparatus / 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 | |||||||||
| Biological species | Homo sapiens (human) / ![]() ![]() Human gammaherpesvirus 8 | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
Authors | Lang K / Aldridge N / Pancera M | |||||||||
| Funding support | United States, 1 items
| |||||||||
Citation | Journal: PLoS Pathog / Year: 2026Title: Monoclonal neutralizing antibodies elicited by infection with Kaposi sarcoma-associated herpesvirus reveal critical sites of vulnerability on gH/gL. Authors: Yu-Hsin Wan / Sara Pernikoff / Nicholas T Aldridge / Kevin Lang / Holly M Dudley / Samuel C Scharffenberger / Gargi Kher / Warren Phipps / Marie Pancera / Jim Boonyaratanakornkit / Andrew T McGuire / ![]() Abstract: Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. A vaccine that prevents KSHV infection or ...Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. A vaccine that prevents KSHV infection or serves in the treatment of KSHV-related diseases represents a critical unmet need, however, the types of immune responses a vaccine should elicit have not been well defined. The gH/gL glycoprotein complex is an important target of KSHV-neutralizing antibodies, but the epitope specificities targeted by these antibodies remain unknown. Here, we isolated 12 gH/gL-specific monoclonal antibodies (mAbs) from KSHV-infected donors and performed structure/function analyses. These mAbs bind recombinant gH/gL with nanomolar affinities and epitope binning analyses revealed that the mAbs bind to 5 epitope clusters on gH/gL. Seven mAbs were able to neutralize KSHV infection of epithelial cell lines. Two potent neutralizing mAbs mapped to the EphA2 binding site as determined by inhibition of the receptor-ligand interaction and negative stain electron microscopy (nsEM) of the mAb/gH/gL complex. The epitopes of other neutralizing mAbs targeting novel sites of vulnerability were determined by a combination of cryogenic electron microscopy and nsEM. Together, these mAbs help to define the relevant epitope targets for KSHV vaccine design, have utility in understanding the role of antibodies in preventing KSHV infection, enable the development of immunotherapy approaches, and provide valuable tools to understand the molecular details of the KSHV entry process. | |||||||||
| History |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_73789.map.gz | 34.6 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-73789-v30.xml emd-73789.xml | 28.1 KB 28.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_73789_fsc.xml | 13.2 KB | Display | FSC data file |
| Images | emd_73789.png | 59.7 KB | ||
| Filedesc metadata | emd-73789.cif.gz | 7.4 KB | ||
| Others | emd_73789_half_map_1.map.gz emd_73789_half_map_2.map.gz | 34.6 MB 34.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-73789 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-73789 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9z3qMC M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|
-
Map
| File | Download / File: emd_73789.map.gz / Format: CCP4 / Size: 37.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.122 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-Half map: #2
| File | emd_73789_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #1
| File | emd_73789_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
-Entire : KSHV glycoprotein heterodimer gHgL 1:1 MLKH3 and MLKH10 FABs
| Entire | Name: KSHV glycoprotein heterodimer gHgL 1:1 MLKH3 and MLKH10 FABs |
|---|---|
| Components |
|
-Supramolecule #1: KSHV glycoprotein heterodimer gHgL 1:1 MLKH3 and MLKH10 FABs
| Supramolecule | Name: KSHV glycoprotein heterodimer gHgL 1:1 MLKH3 and MLKH10 FABs type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 184 KDa |
-Macromolecule #1: MLKH10 Light chain FV
| Macromolecule | Name: MLKH10 Light chain FV / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 12.427777 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: DIVMTQSPDS LSVSLGERAT INCKSSQSVL YSSNNKNYLA WYQQKPGQPP KLLIYWASTR GSGVPDRFSG SGSGTDFTLT ISSLQAEDV AVYYCQQYYN SPRFGGWTKV EIK |
-Macromolecule #2: MLKH10 Heavy chain FV
| Macromolecule | Name: MLKH10 Heavy chain FV / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 13.144362 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: EVQLLESGGG VVRPGGSLRL SCAASGFTFD DYGMSWVRQS PGKGLEWVSG INWNGGSLSY ADSIQGRFTI SRDNAENSLY LQMHSLRAE DTALYYCARV QGSGSYNNFD YWGQGTLVTV SS |
-Macromolecule #3: MLKH3 Light chain FV
| Macromolecule | Name: MLKH3 Light chain FV / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 11.538785 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: DIQLTQSPSS VSASVGDRVT ISCRASQGIS SWLVWYQQKP GKAPKPLIYA ASSLQNGVPA RFSGSGSGTD FTLTINSLQP EDFATYYCQ QANSFPYTFG QGTKLEIK |
-Macromolecule #4: MLKH3 Heavy chain FV
| Macromolecule | Name: MLKH3 Heavy chain FV / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 13.088487 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: EVQLVQSGPE VKKPGSSVKV SCKASGDSFS SNTISWVRQA PGQGLEWMGR LITILGTANY AQKFQGRVTI TADETATTAY MELSSLRSE DTAIYYCAIS EGGYTYDSGS YIWGQGTLVT VSS |
-Macromolecule #5: Envelope glycoprotein H
| Macromolecule | Name: Envelope glycoprotein H / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() Human gammaherpesvirus 8 / Strain: gk18 |
| Molecular weight | Theoretical: 80.917531 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSASATGAL PTTATTITRS ATQLINGRTN LSIELEFNGT SFFLNWQNLL NVITEPALTE LWTSAEVAE DLRVTLKKRQ SLFFPNKTVV ISGDGHRYTC EVPTSSQTYN ITKGFNYSAL PGHLGGFGIN ARLVLGDIFA S KWSLFARD ...String: MDAMKRGLCC VLLLCGAVFV SPSASATGAL PTTATTITRS ATQLINGRTN LSIELEFNGT SFFLNWQNLL NVITEPALTE LWTSAEVAE DLRVTLKKRQ SLFFPNKTVV ISGDGHRYTC EVPTSSQTYN ITKGFNYSAL PGHLGGFGIN ARLVLGDIFA S KWSLFARD TPEYRVFYPM NVMAVKFSIS IGNNESGVAL YGVVSEDFVV VTLHNRSKEA NETASHLLFG LPDSLPSLKG HA TYDELTF ARNAKYALVA ILPKDSYQTL LTENYTRIFL NMTESTPLEF TRTIQTRIVS IEARRACAAQ EAAPDIFLVL FQM LVAHFL VARGIAEHRF VEVDCVCRQY AELYFLRRIS RLCMPTFTTV GYNHTTLGAV AATQIARVSA TKLASLPRSS QETV LAMVQ LGARDGAVPS SILEGIAMVV EHMYTAYTYV YTLGDTERKL MLDIHTVLTD SCPPKDSGVS EKLLRTYLMF TSMCT NIEL GEMIARFSKP DSLNIYRAFS PCFLGLRYDL HPAKLRAEAP QSSALTRTAV ARGTSGFAEL LHALHLDSLN LIPAIN CSK ITADKIIATV PLPHVTYIIS SEALSNAVVY EVSEIFLKSA MFISAIKPDC SGFNFSQIDR HIPIVYNIST PRRGCPL CD SVIMSYDESD GLQSLMYVTN ERVQTNLFLD KSPFFDNNNL HIHYLWLRDN GTVVEIRGMY GSGSGHHHHH HGLNDIFE A QKIEWHE UniProtKB: Envelope glycoprotein H |
-Macromolecule #6: Envelope glycoprotein L
| Macromolecule | Name: Envelope glycoprotein L / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() Human gammaherpesvirus 8 / Strain: gk18 |
| Molecular weight | Theoretical: 18.815754 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSASDGIQY VALPCCAIQA SAASTLPLFF AVHSIHFADP NHCNGVCIAK LRSKTGDITV ETCVNGFNL RSFLVAVVRR LGSWASQENL RLLWYLQRSL TAYTVGFNAT TADSSIHNVN IIIISVGKAM NRTGSVSGSQ T RAKSSSRR AHAGQKGK UniProtKB: Envelope glycoprotein L |
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Concentration | 1 mg/mL |
|---|---|
| Buffer | pH: 7 / Details: 1x TBS |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-
Electron microscopy
| Microscope | TFS GLACIOS |
|---|---|
| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 2 / Number real images: 9372 / Average exposure time: 6.0 sec. / Average electron dose: 50.0 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: 1.0 µm / Nominal magnification: 36000 |
| Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |
+
Image processing
-Atomic model buiding 1
| Initial model |
| ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Software | Name: UCSF ChimeraX (ver. 1.9) | ||||||||||||||
| Refinement | Space: REAL / Protocol: RIGID BODY FIT | ||||||||||||||
| Output model | ![]() PDB-9z3q: |
Movie
Controller
About Yorodumi



Keywords
Homo sapiens (human)

Human gammaherpesvirus 8
Authors
United States, 1 items
Citation






Z (Sec.)
Y (Row.)
X (Col.)




































FIELD EMISSION GUN

