scholarly journals Local stabilization of subunit-subunit contacts causes global destabilization of Hepatitis B virus capsids

2020 ◽  
Author(s):  
Christopher John Schlicksup ◽  
Patrick Laughlin ◽  
Steven Dunkelbarger ◽  
Joseph Che-Yen Wang ◽  
Adam Zlotnick
Keyword(s):  
Electron Microscopy ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Area ◽  
Protein Interaction ◽  
Structural Defects ◽  
Protein Protein Interaction ◽  
Cryo Electron Microscopy ◽  
Virus Capsids ◽  
B Virus

AbstractDevelopment 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 dibenzothiazapine, which 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 pre-formed 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 inter-subunit 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.

Hepatitis B virus X protein modulates peroxisome proliferator-activated receptor γ through protein-protein interaction

FEBS Letters ◽  
2003 ◽  
Vol 557 (1-3) ◽  
pp. 73-80 ◽  
Author(s):  
Youn-Hee Choi ◽  
Ha-il Kim ◽  
Je Kyung Seong ◽  
Dae-Yeul Yu ◽  
Hyeseong Cho ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Protein Interaction ◽  
Peroxisome Proliferator ◽  
X Protein ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Protein Interaction ◽  
B Virus

Visualization and analysis of capsid dimorphism in hepatitis B virus to 17 Å resolution by cryo-electron microscopy

1996 ◽  
Vol 54 ◽  
pp. 916-917
Author(s):  
A. Zlotnick ◽  
N. Cheng ◽  
J.F. Conway ◽  
F.P. Booy ◽  
A.C. Steven ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Amino Acids ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Protein ◽  
Icosahedral Symmetry ◽  
Cryo Electron Microscopy ◽  
B Virus ◽  
Gradient Fractionation ◽  
Protein Constructs

Hepatitis B virus (HBV) is an enveloped virus with an icosahedral capsid. Its homodimeric capsid protein assembles into particles of two sizes - one with T=3 icosahedral symmetry (90 dimers), the other with T=4 symmetry (120 dimers). Both sizes of particle are found in vivo as well as in expression systems. We have developed an in vitro assembly system using purified, bacterially expressed, capsid proteins. Capsids assembled from different protein constructs were studied by cryo-electron microscopy using a Philips CM20 microscope equipped with a field emission gun operating at 120 keV.Capsids assembled from the different protein constructs were assayed by cryo-electron microscopy and sucrose gradient fractionation. Cryo-electron microscopy was required to identify the two different sizes of capsids and the small population of misshapen particles, and also to ascertain the quality of the gradient fractionation (Figure 1, 2). The protein constructs lacked the predominantly basic C-terminal 34 amino acids of the full-length capsid protein (183 amino acids), and were further truncated between residues 138 and 149. Constructs terminating between residue 140 and 149 assembled into mixtures of T=3 and T=4 particles; the smallest construct (138 residues) did not form capsids.

High Resolution Epitope Mapping of the Hepatitis B Virus Capsid by Cryo-Electron Microscopy

1998 ◽  
Vol 4 (S2) ◽  
pp. 966-967
Author(s):  
JF. Conway ◽  
N. Cheng ◽  
A. Zlotnick ◽  
SJ. Stahl ◽  
PT. Wingfield ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Epitope Mapping ◽  
Gold Cluster ◽  
Cysteine Residue ◽  
Cryo Electron Microscopy ◽  
C Terminus ◽  
Cluster Label ◽  
B Virus

The capsid structure of the Hepatitis B virus (HBV) has been studied to resolutions below 10Å by cryo-electron microscopy, revealing much of its a-helical substructure and an apparently novel fold for a capsid protein. Although this represents a significant improvement in resolution for such studies, it is nonetheless still too low for complete tracing of the polypeptide chain. With the aim of establishing fiducial markers to aid in the process of chain-tracing, we have used cryo-microscopy to definitively localize specific peptides on the surface of the capsid. In one such study a gold cluster label was attached to a single cysteine residue engineered on to the C-terminus of the HBcAg assembly domain. The reconstructed density reveals a single gold cluster under each of the icosahedral 5-fold and 2-fold axes and connected to sites at either ends of the undersides of the dimers, thus pin-pointing the location of the C-terminus.

Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy

Nature ◽  
1997 ◽  
Vol 386 (6620) ◽  
pp. 91-94 ◽  
Author(s):  
J. F. Conway ◽  
N. Cheng ◽  
A. Zlotnick ◽  
P. T. Wingfield ◽  
S. J. Stahl ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Capsid ◽  
Helix Bundle ◽  
Cryo Electron Microscopy ◽  
B Virus

scholarly journals Nuclear import of hepatitis B virus capsids and release of the viral genome

2003 ◽  
Vol 100 (17) ◽  
pp. 9849-9854 ◽  
Author(s):  
B. Rabe ◽  
A. Vlachou ◽  
N. Pante ◽  
A. Helenius ◽  
M. Kann
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Import ◽  
Viral Genome ◽  
Virus Capsids ◽  
B Virus

A dimorphism shift of hepatitis B virus capsids in response to ionic conditions

Nanoscale ◽  
2018 ◽  
Vol 10 (36) ◽  
pp. 16984-16989 ◽  
Author(s):  
Xinyu Sun ◽  
Dong Li ◽  
Zhaoshuai Wang ◽  
Qiao Liu ◽  
Yinan Wei ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Capsids ◽  
B Virus

HBV capsid dimorphism regulation through manipulating the rate of capsid nucleation using highly concentrated and/or multivalent counter-cations.

scholarly journals Modeling the functional state of the reverse transcriptase of hepatitis B virus and its application to probing drug-protein interaction

2016 ◽  
Vol 17 (S8) ◽  
Author(s):  
Xiaojun Xu ◽  
Hong Thai ◽  
Kathryn M. Kitrinos ◽  
Guoliang Xia ◽  
Anuj Gaggar ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Functional State ◽  
Protein Interaction ◽  
B Virus

scholarly journals 100 kHz MAS Proton-Detected NMR Spectroscopy of Hepatitis B Virus Capsids

2019 ◽  
Vol 6 ◽  
Author(s):  
Lauriane Lecoq ◽  
Maarten Schledorn ◽  
Shishan Wang ◽  
Susanne Smith-Penzel ◽  
Alexander A. Malär ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Nmr Spectroscopy ◽  
Hepatitis B ◽  
Virus Capsids ◽  
B Virus
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