+Open data
-Basic information
Entry | Database: PDB / ID: 3j6r | ||||||
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Title | Electron cryo-microscopy of Human Papillomavirus Type 16 capsid | ||||||
Components | Major capsid protein L1 | ||||||
Keywords | VIRUS / capsid protein | ||||||
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 | Human papillomavirus type 16 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 9.1 Å | ||||||
Authors | Cardone, G. / Moyer, A.L. / Cheng, N. / Thompson, C.D. / Dvoretzky, I. / Lowy, D.R. / Schiller, J.T. / Steven, A.C. / Buck, C.B. / Trus, B.L. | ||||||
Citation | Journal: mBio / Year: 2014 Title: Maturation of the human papillomavirus 16 capsid. Authors: Giovanni Cardone / Adam L Moyer / Naiqian Cheng / Cynthia D Thompson / Israel Dvoretzky / Douglas R Lowy / John T Schiller / Alasdair C Steven / Christopher B Buck / Benes L Trus / Abstract: Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected ...Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected keratinocytes. Papillomavirus virions are released into the environment through a process known as desquamation, in which keratinocytes lose structural integrity prior to being shed from the surface of the skin. During this process, virions are exposed to an increasingly oxidative environment, leading to their stabilization through the formation of disulfide cross-links between neighboring molecules of the major capsid protein, L1. We used time-lapse cryo-electron microscopy and image analysis to study the maturation of HPV16 capsids assembled in mammalian cells and exposed to an oxidizing environment after cell lysis. Initially, the virion is a loosely connected procapsid that, under in vitro conditions, condenses over several hours into the more familiar 60-nm-diameter papillomavirus capsid. In this process, the procapsid shrinks by ~5% in diameter, its pentameric capsomers change in structure (most markedly in the axial region), and the interaction surfaces between adjacent capsomers are consolidated. A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form. Pseudoatomic modeling based on a 9-Å resolution reconstruction of fully mature capsids revealed C-terminal disulfide-stabilized "suspended bridges" that form intercapsomeric cross-links. The data suggest a model in which procapsids exist in a range of dynamic intermediates that can be locked into increasingly mature configurations by disulfide cross-linking, possibly through a Brownian ratchet mechanism. Importance: Human papillomaviruses (HPVs) cause nearly all cases of cervical cancer, a major fraction of cancers of the penis, vagina/vulva, anus, and tonsils, and genital and nongenital warts. HPV types associated with a high risk of cancer, such as HPV16, are generally transmitted via sexual contact. The nonenveloped virion of HPVs shows a high degree of stability, allowing the virus to persist in an infectious form in environmental fomites. In this study, we used cryo-electron microscopy to elucidate the structure of the HPV16 capsid at different stages of maturation. The fully mature capsid adopts a rigid, highly regular structure stabilized by intermolecular disulfide bonds. The availability of a pseudoatomic model of the fully mature HPV16 virion should help guide understanding of antibody responses elicited by HPV capsid-based vaccines. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 3j6r.cif.gz | 469.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3j6r.ent.gz | 300.4 KB | Display | PDB format |
PDBx/mmJSON format | 3j6r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3j6r_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 3j6r_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 3j6r_validation.xml.gz | 62.3 KB | Display | |
Data in CIF | 3j6r_validation.cif.gz | 105.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j6/3j6r ftp://data.pdbj.org/pub/pdb/validation_reports/j6/3j6r | HTTPS FTP |
-Related structure data
Related structure data | 5932MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 53445.617 Da / Num. of mol.: 6 / Fragment: UNP residues 35-512 / Source method: isolated from a natural source / Source: (natural) Human papillomavirus type 16 / References: UniProt: Q4VRM0, UniProt: P03101*PLUS |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Human Papilloma Virus type 16 capsid / Type: VIRUS |
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Details of virus | Empty: NO / Enveloped: NO / Host category: VERTEBRATES / Isolate: SEROTYPE / Type: VIRION |
Natural host | Organism: Homo sapiens |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: LEICA KF80 / Cryogen name: ETHANE / Details: Plunged into liquid ethane (LEICA KF80) |
-Electron microscopy imaging
Microscopy | Model: FEI/PHILIPS CM200FEG / Date: Feb 2, 2010 |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 120 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 38000 X / Nominal defocus max: 2175 nm / Nominal defocus min: 537 nm / Cs: 2 mm / Camera length: 0 mm |
Specimen holder | Specimen holder model: GATAN LIQUID NITROGEN / Tilt angle max: 0 ° / Tilt angle min: 0 ° |
Image recording | Film or detector model: KODAK SO-163 FILM |
Image scans | Num. digital images: 20 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
-Processing
EM software |
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CTF correction | Details: each micrograph | ||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||
3D reconstruction | Method: projection-matching, direct Fourier inversion / Resolution: 9.1 Å / Resolution method: FSC 0.33 CUT-OFF / Num. of particles: 5952 / Nominal pixel size: 1.41 Å / Actual pixel size: 1.41 Å / Details: (Single particle--Applied symmetry: I) / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL Details: REFINEMENT PROTOCOL--flexible DETAILS--Rigid fitting of domain copies in asymmetric unit, followed by molecular dynamics-based flexible fitting, adding symmetry as constraint | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 1DZL Pdb chain-ID: A / Accession code: 1DZL / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refinement step | Cycle: LAST
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