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- EMDB-7136: High-Resolution Structure Analysis of Antibody V5 and U4 Conforma... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7136 | |||||||||
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Title | High-Resolution Structure Analysis of Antibody V5 and U4 Conformational Epitope on Human Papillomavirus 16 | |||||||||
![]() | Antibody V5 and U4 Conformational Epitope on Human Papillomavirus 16 | |||||||||
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![]() | HPV16 / H16.V5 / Fab / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() T=7 icosahedral viral capsid / endocytosis involved in viral entry into host cell / virion attachment to host cell / host cell nucleus / structural molecule activity Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.7 Å | |||||||||
![]() | Guan J / Bywaters SM / Brendle SA / Ashley RE / Makhov AM / Conway JF / Christenson ND / Hafenstein S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: High-Resolution Structure Analysis of Antibody V5 and U4 Conformational Epitopes on Human Papillomavirus 16. Authors: Jian Guan / Stephanie M Bywaters / Sarah A Brendle / Robert E Ashley / Alexander M Makhov / James F Conway / Neil D Christensen / Susan Hafenstein / ![]() Abstract: Cancers attributable to human papillomavirus (HPV) place a huge burden on the health of both men and women. The current commercial vaccines are genotype specific and provide little therapeutic ...Cancers attributable to human papillomavirus (HPV) place a huge burden on the health of both men and women. The current commercial vaccines are genotype specific and provide little therapeutic benefit to patients with existing HPV infections. Identifying the conformational epitopes on the virus capsid supports the development of improved recombinant vaccines to maximize long-term protection against multiple types of HPV. Fragments of antibody (Fab) digested from the neutralizing monoclonal antibodies H16.V5 (V5) and H16.U4 (U4) were bound to HPV16 capsids and the structures of the two virus-Fab complexes were solved to near atomic resolution using cryo-electron microscopy. The structures reveal virus conformational changes, the Fab-binding mode to the capsid, the residues comprising the epitope and indicate a potential interaction of U4 with the minor structural protein, L2. Competition enzyme-linked immunosorbent assay (ELISA) showed V5 outcompetes U4 when added sequentially, demonstrating a steric interference even though the footprints do not overlap. Combined with our previously reported immunological and structural results, we propose that the virus may initiate host entry through an interaction between the icosahedral five-fold vertex of the capsid and receptors on the host cell. The highly detailed epitopes identified for the two antibodies provide a framework for continuing biochemical, genetic and biophysical studies. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1.1 GB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.9 KB 12.9 KB | Display Display | ![]() |
Images | ![]() | 333.9 KB | ||
Filedesc metadata | ![]() | 5.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6bspMC ![]() 8243C ![]() 6bt3C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Antibody V5 and U4 Conformational Epitope on Human Papillomavirus 16 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.147 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Human papillomavirus type 16 / Antibody complex
Entire | Name: Human papillomavirus type 16 / Antibody complex |
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Components |
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-Supramolecule #1: Human papillomavirus type 16 / Antibody complex
Supramolecule | Name: Human papillomavirus type 16 / Antibody complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Antibody U4
Supramolecule | Name: Antibody U4 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: Human papillomavirus type 16
Supramolecule | Name: Human papillomavirus type 16 / type: virus / ID: 3 / Parent: 1 / Macromolecule list: #3 / NCBI-ID: 333760 / Sci species name: Human papillomavirus type 16 / Virus type: VIRION / Virus isolate: SEROCOMPLEX / Virus enveloped: No / Virus empty: No |
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Host (natural) | Organism: ![]() |
-Macromolecule #1: U4 Heavy chain
Macromolecule | Name: U4 Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 12.108347 KDa |
Sequence | String: SGGGLVKPGG SLKLSCEASG FTFSSYAMSW VRQTPEKRLE WVASISSGGN THYPDSVKGR FTISRDNARN ILYLQMSSLR SEDTAMYYC ARGLYYGYDE GSDFDYWGQG |
-Macromolecule #2: U4 Light chain
Macromolecule | Name: U4 Light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 12.09953 KDa |
Sequence | String: DIVMSQSPSS LAVSVGEKVT MSCKSSQSLL YSNTQKNYLA WYQQKPGQSP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT ISSVKAEDL AVYYCQQYYS YPLTFGAGTK L |
-Macromolecule #3: Major capsid protein L1
Macromolecule | Name: Major capsid protein L1 / type: protein_or_peptide / ID: 3 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 52.387277 KDa |
Sequence | String: YLPPVPVSKV VSTDEYVART NIYYHAGTSR LLAVGHPYFP IKKPNNNKIL VPKVSGLQYR VFRIHLPDPN KFGFPDTSFY NPDTQRLVW ACVGVEVGRG QPLGVGISGH PLLNKLDDTE NASAYAANAG VDNRECISMD YKQTQLCLIG CKPPIGEHWG K GSPCTNVA ...String: YLPPVPVSKV VSTDEYVART NIYYHAGTSR LLAVGHPYFP IKKPNNNKIL VPKVSGLQYR VFRIHLPDPN KFGFPDTSFY NPDTQRLVW ACVGVEVGRG QPLGVGISGH PLLNKLDDTE NASAYAANAG VDNRECISMD YKQTQLCLIG CKPPIGEHWG K GSPCTNVA VNPGDCPPLE LINTVIQDGD MVDTGFGAMD FTTLQANKSE VPLDICTSIC KYPDYIKMVS EPYGDSLFFY LR REQMFVR HLFNRAGAVG ENVPDDLYIK GSGSTANLAS SNYFPTPSGS MVTSDAQIFN KPYWLQRAQG HNNGICWGNQ LFV TVVDTT RSTNMSLCAA ISTSETTYKN TNFKEYLRHG EEYDLQFIFQ LCKITLTADV MTYIHSMNST ILEDWNFGLQ PPPG GTLED TYRFVTSQAI ACQKHTPPAP KEDPLKKYTF WEVNLKEKFS ADLDQFPLGR KFLLQAGLKA KPKF UniProtKB: Major capsid protein L1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: FEI FALCON II (4k x 4k) / #0 - Average electron dose: 7.0 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: FEI FALCON II (4k x 4k) / #1 - Average electron dose: 7.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |