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Yorodumi- EMDB-30787: 2-fold subparticles refinement of human papillomavirus type 58 ps... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30787 | |||||||||
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Title | 2-fold subparticles refinement of human papillomavirus type 58 pseudovirus in complexed with the Fab fragment of A4B4 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information T=7 icosahedral viral capsid / endocytosis involved in viral entry into host cell / host cell nucleus / virion attachment to host cell / structural molecule activity Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / Human papillomavirus type 58 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.19 Å | |||||||||
Authors | He MZ / Chi X / Zha ZH / Zheng QB / Gu Y / Li SW / Xia NS | |||||||||
Funding support | China, 1 items
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Citation | Journal: J Virol / Year: 2021 Title: Structural basis for the shared neutralization mechanism of three classes of human papillomavirus type 58 antibodies with disparate modes of binding. Authors: Maozhou He / Xin Chi / Zhenghui Zha / Yunbing Li / Jie Chen / Yang Huang / Shiwen Huang / Miao Yu / Zhiping Wang / Shuo Song / Xinlin Liu / Shuangping Wei / Zekai Li / Tingting Li / Yingbin ...Authors: Maozhou He / Xin Chi / Zhenghui Zha / Yunbing Li / Jie Chen / Yang Huang / Shiwen Huang / Miao Yu / Zhiping Wang / Shuo Song / Xinlin Liu / Shuangping Wei / Zekai Li / Tingting Li / Yingbin Wang / Hai Yu / Qinjian Zhao / Jun Zhang / Qingbing Zheng / Ying Gu / Shaowei Li / Ningshao Xia / Abstract: Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and ...Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5 Å) structure of the complete HPV58 pseudovirus (PsV58) using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3 and A4B4) were selected through clustering from a nAb panel against HPV58. Bypassing the steric hindrance and symmetry-mismatch in the HPV Fab-capsid immune-complex, we present three different neutralizing epitopes in the PsV58, and show that, despite differences in binding, these nAbs share a common neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research. Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially within Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2 and A4B4) from three different groups share a common neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we identify that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a common neutralization mechanism. These results provide new insight into the understanding of HPV58 infection. | |||||||||
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_30787.map.gz | 262.3 MB | EMDB map data format | |
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Header (meta data) | emd-30787-v30.xml emd-30787.xml | 13.7 KB 13.7 KB | Display Display | EMDB header |
Images | emd_30787.png | 167.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30787 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30787 | HTTPS FTP |
-Validation report
Summary document | emd_30787_validation.pdf.gz | 643.8 KB | Display | EMDB validaton report |
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Full document | emd_30787_full_validation.pdf.gz | 643.4 KB | Display | |
Data in XML | emd_30787_validation.xml.gz | 7.7 KB | Display | |
Data in CIF | emd_30787_validation.cif.gz | 8.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30787 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30787 | HTTPS FTP |
-Related structure data
Related structure data | 7dnlMC 7dn5C 7dnhC 7dnkC 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_30787.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.121 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Human papillomavirus type 58 in complexed with the Fab fragment o...
Entire | Name: Human papillomavirus type 58 in complexed with the Fab fragment of A4B4 |
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Components |
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-Supramolecule #1: Human papillomavirus type 58 in complexed with the Fab fragment o...
Supramolecule | Name: Human papillomavirus type 58 in complexed with the Fab fragment of A4B4 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #2: Fab fragment of A4B4
Supramolecule | Name: Fab fragment of A4B4 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Human papillomavirus type 58 |
-Supramolecule #3: Human papillomavirus type 58
Supramolecule | Name: Human papillomavirus type 58 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: The light chain of A4B4 Fab fragment
Macromolecule | Name: The light chain of A4B4 Fab fragment / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 24.455184 KDa |
Sequence | String: DIVMSQSPSS LAVSVGEKVT MSCKSSQSLL YSSIQKNYLA WYQQKPGQSP KLLIYWASIR ESGVPDRFTG SGSGTDFTLT ISSVKAEDL AVYYCQRYYG YPWTFGGGTK LEIKRADAAP TVSIFPPSSE QLTSGGASVV CFLNNFYPKD INVKWKIDGS E RQNGVLNS ...String: DIVMSQSPSS LAVSVGEKVT MSCKSSQSLL YSSIQKNYLA WYQQKPGQSP KLLIYWASIR ESGVPDRFTG SGSGTDFTLT ISSVKAEDL AVYYCQRYYG YPWTFGGGTK LEIKRADAAP TVSIFPPSSE QLTSGGASVV CFLNNFYPKD INVKWKIDGS E RQNGVLNS WTDQDSKDST YSMSSTLTLT KDEYERHNSY TCEATHKTST SPIVKSFNRN EC |
-Macromolecule #2: The heavy chain of 2H3 Fab fragment
Macromolecule | Name: The heavy chain of 2H3 Fab fragment / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.084834 KDa |
Sequence | String: QVTLKESGPG ILQPSQTLSL TCSFSGFSLS TSGMGVGWIR QPSGKGLEWL AHIWWNDDKN YHPALKSRLT ISKDTSSNRV FLNIASVDT ADTATYYCAR IHYVTDALDY WGQGTSVTVS AKTTAPSVYP LAPVCGDTTG SSVTLGCLVK GYFPEPVTLT W NSGSLSSG ...String: QVTLKESGPG ILQPSQTLSL TCSFSGFSLS TSGMGVGWIR QPSGKGLEWL AHIWWNDDKN YHPALKSRLT ISKDTSSNRV FLNIASVDT ADTATYYCAR IHYVTDALDY WGQGTSVTVS AKTTAPSVYP LAPVCGDTTG SSVTLGCLVK GYFPEPVTLT W NSGSLSSG VHTFPAVLQS DLYTLSSSVT VTSSTWPSQS ITCNVAHPAS STKVDKKI |
-Macromolecule #3: Major capsid protein L1
Macromolecule | Name: Major capsid protein L1 / type: protein_or_peptide / ID: 3 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: Human papillomavirus type 58 |
Molecular weight | Theoretical: 59.103199 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVLILCCTLA ILFCVADVNV FHIFLQMSVW RPSEATVYLP PVPVSKVVST DEYVSRTSIY YYAGSSRLLA VGNPYFSIKS PNNNKKVLV PKVSGLQYRV FRVRLPDPNK FGFPDTSFYN PDTQRLVWAC VGLEIGRGQP LGVGVSGHPY LNKFDDTETS N RYPAQPGS ...String: MVLILCCTLA ILFCVADVNV FHIFLQMSVW RPSEATVYLP PVPVSKVVST DEYVSRTSIY YYAGSSRLLA VGNPYFSIKS PNNNKKVLV PKVSGLQYRV FRVRLPDPNK FGFPDTSFYN PDTQRLVWAC VGLEIGRGQP LGVGVSGHPY LNKFDDTETS N RYPAQPGS DNRECLSMDY KQTQLCLIGC KPPTGEHWGK GVACNNNAAA TDCPPLELFN SIIEDGDMVD TGFGCMDFGT LQ ANKSDVP IDICNSTCKY PDYLKMASEP YGDSLFFFLR REQMFVRHFF NRAGKLGEAV PDDLYIKGSG NTAVIQSSAF FPT PSGSIV TSESQLFNKP YWLQRAQGHN NGICWGNQLF VTVVDTTRST NMTLCTEVTK EGTYKNDNFK EYVRHVEEYD LQFV FQLCK ITLTAEIMTY IHTMDSNILE DWQFGLTPPP SASLQDTYRF VTSQAITCQK TAPPKEKEDP LNKYTFWEVN LKEKF SADL DQFPLGRKFL LQSGLKAKPR LKRSAPTTRA PSTKRKKVKK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI F30 |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.19 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 94862 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |