+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9031 | |||||||||
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Title | Cryo-EM structure of Woodchuck hepatitis virus capsid | |||||||||
Map data | Woodchuck hepatitis virus capsid | |||||||||
Sample |
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Keywords | WHV / Capsid structure / VIRUS LIKE PARTICLE | |||||||||
Function / homology | Function and homology information virus-mediated perturbation of host defense response => GO:0019049 / microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / : / viral penetration into host nucleus / host cell cytoplasm / symbiont entry into host cell / virus-mediated perturbation of host defense response / host cell nucleus / structural molecule activity ...virus-mediated perturbation of host defense response => GO:0019049 / microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / : / viral penetration into host nucleus / host cell cytoplasm / symbiont entry into host cell / virus-mediated perturbation of host defense response / host cell nucleus / structural molecule activity / DNA binding / RNA binding / extracellular region Similarity search - Function | |||||||||
Biological species | Woodchuck hepatitis virus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.52 Å | |||||||||
Authors | Zhao Z / Wang JC | |||||||||
Funding support | United States, 1 items
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Citation | Journal: J Virol / Year: 2019 Title: Structural Differences between the Woodchuck Hepatitis Virus Core Protein in the Dimer and Capsid States Are Consistent with Entropic and Conformational Regulation of Assembly. Authors: Zhongchao Zhao / Joseph Che-Yen Wang / Giovanni Gonzalez-Gutierrez / Balasubramanian Venkatakrishnan / Roi Asor / Daniel Khaykelson / Uri Raviv / Adam Zlotnick / Abstract: Hepadnaviruses are hepatotropic enveloped DNA viruses with an icosahedral capsid. Hepatitis B virus (HBV) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (WHV), ...Hepadnaviruses are hepatotropic enveloped DNA viruses with an icosahedral capsid. Hepatitis B virus (HBV) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (WHV), an HBV homologue, has been an important model system for drug development. The dimeric capsid protein (Cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. Purified HBV and WHV Cp spontaneously assemble into 120-dimer capsids. Though they have 65% identity, WHV Cp has error-prone assembly with stronger protein-protein association. We have taken advantage of the differences in assemblies to investigate the basis of assembly regulation. We determined the structures of the WHV capsid to 4.5-Å resolution by cryo-electron microscopy (cryo-EM) and of the WHV Cp dimer to 2.9-Å resolution by crystallography and examined the biophysical properties of the dimer. We found, in dimer, that the subdomain that makes protein-protein interactions is partially disordered and rotated 21° from its position in capsid. This subdomain is susceptible to proteolysis, consistent with local disorder. WHV assembly shows similar susceptibility to HBV antiviral molecules, suggesting that HBV assembly follows similar transitions. These data show that there is an entropic cost for assembly that is compensated for by the energetic gain of burying hydrophobic interprotein contacts. We propose a series of stages in assembly that incorporate a disorder-to-order transition and structural shifts. We suggest that a cascade of structural changes may be a common mechanism for regulating high-fidelity capsid assembly in HBV and other viruses. Virus capsids assemble spontaneously with surprisingly high fidelity. This requires strict geometry and a narrow range of association energies for these protein-protein interactions. It was hypothesized that requiring subunits to undergo a conformational change to become assembly active could regulate assembly by creating an energetic barrier and attenuating association. We found that woodchuck hepatitis virus capsid protein undergoes structural transitions between its dimeric and its 120-dimer capsid states. It is likely that the closely related hepatitis B virus capsid protein undergoes similar structural changes, which has implications for drug design. Regulation of assembly by structural transition may be a common mechanism for many viruses. | |||||||||
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_9031.map.gz | 14.7 MB | EMDB map data format | |
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Header (meta data) | emd-9031-v30.xml emd-9031.xml | 10.4 KB 10.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9031_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_9031.png | 89.9 KB | ||
Masks | emd_9031_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-9031.cif.gz | 5.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9031 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9031 | HTTPS FTP |
-Related structure data
Related structure data | 6edjMC 6ecsC 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_9031.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Woodchuck hepatitis virus capsid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.72 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_9031_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Woodchuck hepatitis virus
Entire | Name: Woodchuck hepatitis virus |
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Components |
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-Supramolecule #1: Woodchuck hepatitis virus
Supramolecule | Name: Woodchuck hepatitis virus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 35269 / Sci species name: Woodchuck hepatitis virus / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: OTHER / Virus enveloped: No / Virus empty: Yes |
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-Macromolecule #1: External core antigen
Macromolecule | Name: External core antigen / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Woodchuck hepatitis virus |
Molecular weight | Theoretical: 17.126465 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MDIDPYKEFG SSYQLLNFLP LDFFPDLNAL VDTATALYEE ELTGREHCSP HHTAIRQALV CWDELTKLIA WMSSNITSEQ VRTIIVNHV NDTWGLKVRQ SLWFHLSCLT FGQHTVQEFL VSFGVWIRTP APYRPPNAPI LSTLPEHTVI UniProtKB: External core antigen |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.5 |
Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / 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: Titan Krios / Image courtesy: FEI Company |