6wfs

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==Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the antiviral molecule DBT1==
==Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the antiviral molecule DBT1==
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<StructureSection load='6wfs' size='340' side='right'caption='[[6wfs]]' scene=''>
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<StructureSection load='6wfs' size='340' side='right'caption='[[6wfs]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WFS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WFS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6wfs]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hbv-d Hbv-d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WFS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WFS FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wfs OCA], [http://pdbe.org/6wfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wfs RCSB], [http://www.ebi.ac.uk/pdbsum/6wfs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wfs ProSAT]</span></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U0A:11-oxo-N-[2-(4-sulfamoylphenyl)ethyl]-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide'>U0A</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wfs OCA], [http://pdbe.org/6wfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wfs RCSB], [http://www.ebi.ac.uk/pdbsum/6wfs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wfs ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/CAPSD_HBVD1 CAPSD_HBVD1]] Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions (By similarity).<ref>PMID:7711014</ref> Encapsidates hepatitis delta genome (By similarity).<ref>PMID:7711014</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Development of antiviral molecules that bind virion is a strategy that remains in its infancy, and the details of their mechanisms are poorly understood. Here we investigate the behavior of DBT1, a dibenzothiazepine that specifically interacts with the capsid protein of hepatitis B virus (HBV). We found that DBT1 stabilizes protein-protein interaction, accelerates capsid assembly, and can induce formation of aberrant particles. Paradoxically, DBT1 can cause preformed capsids to dissociate. These activities may lead to (i) assembly of empty and defective capsids, inhibiting formation of new virus, and (ii) disruption of mature viruses, which are metastable, to inhibit new infection. Using cryo-electron microscopy, we observed that DBT1 led to asymmetric capsids where well-defined DBT1 density was bound at all intersubunit contacts. These results suggest that DBT1 can support assembly by increasing buried surface area but induce disassembly of metastable capsids by favoring asymmetry to induce structural defects.
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Local Stabilization of Subunit-Subunit Contacts Causes Global Destabilization of Hepatitis B Virus Capsids.,Schlicksup CJ, Laughlin P, Dunkelbarger S, Wang JC, Zlotnick A ACS Chem Biol. 2020 Jun 19;15(6):1708-1717. doi: 10.1021/acschembio.0c00320. Epub, 2020 May 19. PMID:32369333<ref>PMID:32369333</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6wfs" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Hbv-d]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Schlicksup, C, Laughlin, P, Dunkelbarger, S, Wang, JC, Zlotnick, A]]
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[[Category: Dunkelbarger, S]]
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[[Category: Laughlin, P]]
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[[Category: Schlicksup, C]]
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[[Category: Wang, J C]]
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[[Category: Zlotnick, A]]
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[[Category: Antiviral]]
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[[Category: Capsid]]
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[[Category: Hbv]]
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[[Category: Virus like particle]]

Revision as of 09:02, 20 July 2020

Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the antiviral molecule DBT1

PDB ID 6wfs

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