View source for 6cwt


==Hepatitis B core-antigen in complex with Fab e21==
<StructureSection load='6cwt' size='340' side='right' caption='[[6cwt]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cwt]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CWT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CWT FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cwt OCA], [http://pdbe.org/6cwt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cwt RCSB], [http://www.ebi.ac.uk/pdbsum/6cwt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cwt ProSAT]</span></td></tr>
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== Function ==
[[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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== Publication Abstract from PubMed ==
Hepatitis B virus (HBV) is the leading cause of liver disease worldwide. While an adequate vaccine is available, current treatment options are limited, not highly effective, and associated with adverse effects, encouraging the development of alternative therapeutics. The HBV core gene encodes two different proteins: core, which forms the viral nucleocapsid, and pre-core, which serves as an immune modulator with multiple points of action. The two proteins mostly have the same sequence, although they differ at their N and C termini and in their dimeric arrangements. Previously, we engineered two human-framework antibody fragments (Fab/scFv) with nano- to picomolar affinities for both proteins. Here, by means of X-ray crystallography, analytical ultracentrifugation, and electron microscopy, we demonstrate that the antibodies have non-overlapping epitopes and effectively block biologically important assemblies of both proteins. These properties, together with the anticipated high tolerability and long half-lives of the antibodies, make them promising therapeutics.

Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition.,Eren E, Watts NR, Dearborn AD, Palmer IW, Kaufman JD, Steven AC, Wingfield PT Structure. 2018 Jul 17. pii: S0969-2126(18)30244-2. doi:, 10.1016/j.str.2018.06.012. PMID:30100358<ref>PMID:30100358</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Eren, E]]
[[Category: Steven, A C]]
[[Category: Wingfield, P T]]
[[Category: Core dimer]]
[[Category: Fab]]
[[Category: Hepatitis b virus]]
[[Category: Nucleocapsid]]
[[Category: Viral protein]]
[[Category: Viral protein-immune system complex]]