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6cwt

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Revision as of 08:34, 17 October 2018

Hepatitis B core-antigen in complex with Fab e21

Structural highlights

6cwt is a 6 chain structure with sequence from European rabbit and Hbv-d. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] Encapsidates hepatitis delta genome (By similarity).^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wingfield PT, Stahl SJ, Williams RW, Steven AC. Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis, and in vitro capsid assembly. Biochemistry. 1995 Apr 18;34(15):4919-32. PMID:7711014
↑ Wingfield PT, Stahl SJ, Williams RW, Steven AC. Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis, and in vitro capsid assembly. Biochemistry. 1995 Apr 18;34(15):4919-32. PMID:7711014
↑ Eren E, Watts NR, Dearborn AD, Palmer IW, Kaufman JD, Steven AC, Wingfield PT. Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition. Structure. 2018 Jul 17. pii: S0969-2126(18)30244-2. doi:, 10.1016/j.str.2018.06.012. PMID:30100358 doi:http://dx.doi.org/10.1016/j.str.2018.06.012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cwt"

@@ Line 3: / Line 3: @@
 <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>
+<table><tr><td colspan='2'>[[6cwt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Hbv-d Hbv-d]. 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>
 </table>
@@ Line 21: / Line 21: @@
 __TOC__
 </StructureSection>
+[[Category: European rabbit]]
+[[Category: Hbv-d]]
 [[Category: Eren, E]]
 [[Category: Steven, A C]]

6cwt

From Proteopedia

Revision as of 08:34, 17 October 2018

Hepatitis B core-antigen in complex with Fab e21

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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