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6bvf

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Revision as of 08:20, 27 November 2019

Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the fluorescent allosteric modulator HAP-TAMRA

Structural highlights

6bvf is a 4 chain structure with sequence from Hbv-d. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function. Heteroaryldihydropyrimidines (HAPs) inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp), suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP-TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids. Kinetic and spectroscopic studies imply that HAP-binding sites are usually not available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA asymmetrically deformed capsids, creating a heterogeneous array of sharp angles, flat regions, and outright breaks. To achieve high resolution reconstruction (<4 A), we introduced a disulfide crosslink that rescued particle symmetry. We deduced that HAP-TAMRA caused quasi-sixfold vertices to become flatter and fivefold more angular. This transition led to asymmetric faceting. That a disordered crosslink could rescue symmetry implies that capsids have tensegrity properties. Capsid distortion and disruption is a new mechanism by which molecules like the HAPs can block HBV infection.

Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids.,Schlicksup CJ, Wang JC, Francis S, Venkatakrishnan B, Turner WW, VanNieuwenhze M, Zlotnick A Elife. 2018 Jan 29;7. pii: 31473. doi: 10.7554/eLife.31473. PMID:29377794^[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
↑ Schlicksup CJ, Wang JC, Francis S, Venkatakrishnan B, Turner WW, VanNieuwenhze M, Zlotnick A. Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids. Elife. 2018 Jan 29;7. pii: 31473. doi: 10.7554/eLife.31473. PMID:29377794 doi:http://dx.doi.org/10.7554/eLife.31473

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/6bvf"

@@ Line 1: / Line 1: @@
 ==Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the fluorescent allosteric modulator HAP-TAMRA==
-<StructureSection load='6bvf' size='340' side='right' caption='[[6bvf]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
+<StructureSection load='6bvf' size='340' side='right'caption='[[6bvf]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6bvf]] 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=6BVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BVF FirstGlance]. <br>
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Hbv-d]]
+[[Category: Large Structures]]
 [[Category: Schlicksup, C]]
 [[Category: Wang, J C]]

6bvf

From Proteopedia

Revision as of 08:20, 27 November 2019

Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the fluorescent allosteric modulator HAP-TAMRA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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