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- EMDB-63198: Post-fusion ectodomain of KSHV gB in complex with 2C4 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-63198
TitlePost-fusion ectodomain of KSHV gB in complex with 2C4 Fab
Map data
Sample
  • Complex: Complex of KSHV post-fusion gB with 2C4 Fab
    • Protein or peptide: Core gene UL27 family protein
    • Protein or peptide: 2C4 Fab H chain
    • Protein or peptide: 2C4 Fab L chain
KeywordsKSHV / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


host cell endosome / host cell Golgi apparatus / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / membrane
Similarity search - Function
: / Herpesvirus Glycoprotein B / Herpesvirus Glycoprotein B, PH-like domain 1 / Herpesvirus Glycoprotein B, PH-like domain 2 / Herpesvirus Glycoprotein B, PH-like domain 2 superfamily / Herpesvirus Glycoprotein B ectodomain / Herpesvirus Glycoprotein B / Herpesvirus Glycoprotein B PH-like domain
Similarity search - Domain/homology
Core gene UL27 family protein
Similarity search - Component
Biological speciesHomo sapiens (human) / Human gammaherpesvirus 8
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsFang XY / Sun C / Xie C / Zeng MS / Liu Z
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82030046 China
CitationJournal: Adv Sci (Weinh) / Year: 2025
Title: Structure and Antigenicity of Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein B.
Authors: Xin-Yan Fang / Cong Sun / Chu Xie / Bing-Zhen Cheng / Zheng-Zhou Lu / Ge-Xin Zhao / Sen-Fang Sui / Mu-Sheng Zeng / Zheng Liu /
Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the human γ-herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B-cell ...Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the human γ-herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B-cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or specific therapeutics are currently available to prevent or treat KSHV infection. Similar to other herpesviruses, KSHV depends on the envelope glycoprotein B (gB) for host receptor recognition and membrane fusion initiation, making gB a prime target for antiviral antibody or vaccine development. In this study, the high-resolution cryo-electron microscopy (cryo-EM) structure of KSHV gB is presented, revealing a unique trimeric conformation resembling the postfusion state observed in other herpesviruses. Additionally, the structure of the non-neutralizing monoclonal antibody 2C4 bound to KSHV gB domain IV is resolved. The comparative sequence and structure analyses reveal significant homology in neutralizing epitopes between KSHV and Epstein-Barr virus (EBV) gB, indicating a potential pathway for the development of broad-spectrum antiviral strategies. These findings provide a foundation for a deeper understanding of KSHV's infectious mechanism and pave the way for the creation of universal interventions against the human γ-herpesviruses.
History
DepositionJan 17, 2025-
Header (metadata) releaseMar 5, 2025-
Map releaseMar 5, 2025-
UpdateSep 17, 2025-
Current statusSep 17, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_63198.png

Downloads & links

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Map

FileDownload / File: emd_63198.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 448 pix.
= 383.04 Å		0.86 Å/pix.
x 448 pix.
= 383.04 Å		0.86 Å/pix.
x 448 pix.
= 383.04 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.855 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.222
Minimum - Maximum-0.14008284 - 0.64952576
Average (Standard dev.)0.00041443564 (±0.020814853)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions448448448
Spacing448448448
CellA=B=C: 383.04 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_63198_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_63198_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of KSHV post-fusion gB with 2C4 Fab

EntireName: Complex of KSHV post-fusion gB with 2C4 Fab
Components
  • Complex: Complex of KSHV post-fusion gB with 2C4 Fab
    • Protein or peptide: Core gene UL27 family protein
    • Protein or peptide: 2C4 Fab H chain
    • Protein or peptide: 2C4 Fab L chain

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Supramolecule #1: Complex of KSHV post-fusion gB with 2C4 Fab

SupramoleculeName: Complex of KSHV post-fusion gB with 2C4 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Core gene UL27 family protein

MacromoleculeName: Core gene UL27 family protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human gammaherpesvirus 8
Molecular weightTheoretical: 73.137594 KDa
Recombinant expressionOrganism: Human gammaherpesvirus 8
SequenceString: MTPRSRLATL GTVILLVCFC AGAAHSRGDT FQTSSSPTPP GSSSKAPTKP GEEASGPKSV DFYQFRVCSA SITGELFRFN LEQTCPDTK DKYHQEGILL VYKKNIVPHI FKVRRYRKIA TSVTVYRGHR ESAITNKYEL PRPVPLYEIS HMDSTYQCFS S MKVNVNGV ...String:
MTPRSRLATL GTVILLVCFC AGAAHSRGDT FQTSSSPTPP GSSSKAPTKP GEEASGPKSV DFYQFRVCSA SITGELFRFN LEQTCPDTK DKYHQEGILL VYKKNIVPHI FKVRRYRKIA TSVTVYRGHR ESAITNKYEL PRPVPLYEIS HMDSTYQCFS S MKVNVNGV ENTFTDRDDV NTTVFLQPVE GLTDNIQRYF SQPVIYAEPG RVEATYRVRT TVNCEIVDMI ARSAEPYNYF VT SLGDTVE VSPFCYNESS CSTTPSNKNG LSVQVVLNHT VVTYSDRGTS PTPQNRIFVE TGAYTLSWAS ESKTTAVCPL ALW KTFPRS IQTTHEDSFH FVANEITATF TAPLTPVANF TDTYSCLTSD INTTLNASKA KLASTHVPNG TVQYFHTTGG LYLV WQPMS AINLTHAQGD SGNPTSSPPP SASPMTTSAS RGGSGGASTA AAGGGGSTDN LSYTQLQFAY DKLRDGINQV LEELS RAWC REQVRDNLMW YELSKINPTS VMTAIYGRPV SAKFVGDAIS VTECINVDQS SVNIHKSLRT NSKDVCYARP LVTFKF LNS SNLFTGQLGA RNEIILTNNQ VETCKDTCEH YFITRNETLV YKDYAYLRTI NTTDISTLNT FIALNLSFIQ NIDFKAI EL YSSAEKRLAS SGSHHHHHH

UniProtKB: Core gene UL27 family protein

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Macromolecule #2: 2C4 Fab H chain

MacromoleculeName: 2C4 Fab H chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.85123 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSQ VQLVQSGAEL KTPGSSVKVS CKASGGTFSS NTVSWLRQAP GQGLEWMGRI IPIVDVTNYA QKFQGRVKI TADKSTTTAY MQLSSLRSED TAVYFCARDD AIDPFSYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT A ALGCLVKD ...String:
MGWSCIILFL VATATGVHSQ VQLVQSGAEL KTPGSSVKVS CKASGGTFSS NTVSWLRQAP GQGLEWMGRI IPIVDVTNYA QKFQGRVKI TADKSTTTAY MQLSSLRSED TAVYFCARDD AIDPFSYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT A ALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKRVEPK SC DKGSHHH HHHHH

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Macromolecule #3: 2C4 Fab L chain

MacromoleculeName: 2C4 Fab L chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.856516 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGSWAS SELSQPASVS GSPGQSITIS CTGTSSDVGA YNFVSWYQQH PGKAPKLMIY DVTKWPSGVS NRFSGSKSG NTASLTISGL QAEDEADYYC SSYASSNTYV FGTGTKLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI S DFYPGAVT ...String:
MGWSCIILFL VATATGSWAS SELSQPASVS GSPGQSITIS CTGTSSDVGA YNFVSWYQQH PGKAPKLMIY DVTKWPSGVS NRFSGSKSG NTASLTISGL QAEDEADYYC SSYASSNTYV FGTGTKLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI S DFYPGAVT VAWKADSSPV KAGVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (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: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 339379
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

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