scholarly journals Asymmetrizing an icosahedral virus capsid by hierarchical assembly of subunits with designed asymmetry

2020 ◽  
Author(s):  
Zhongchao Zhao ◽  
Joseph Wang ◽  
Mi Zhang ◽  
Nicholas Lyktey ◽  
Martin Jarrold ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Virus Capsid ◽  
Viral Capsids ◽  
Hierarchical Assembly ◽  
Assembly Pathway ◽  
B Virus ◽  
Icosahedral Virus ◽  
Programmed Assembly ◽  
Virus Capsid Protein

Abstract Symmetrical protein complexes are ubiquitous in natural biological systems. Many have been reengineered in vitro for chemical and medical applications. Symmetrical viral capsids and their assembly are frequent platforms for these investigations. Lacking a means to create asymmetric capsids may limit broader applications. Here, starting with the homodimeric Hepatitis B Virus capsid protein, we developed a heterodimer, designed a hierarchical assembly pathway, and produced asymmetric capsids. We showed that the heterodimers assemble into hexamers, and such preformed hexamers can nucleate co-assembly, leading to “Janus” capsids with two discrete patches. We removed the hexamer patches specifically and observed asymmetric holey capsids by cryo-EM reconstruction. The resulting holes can be refilled with new engineered dimers. This programmed assembly pathway provides windows for specific engineering and modification inside and outside of the capsid. This strategy can also be generalized to other capsid assembly systems.

scholarly journals Asymmetrizing an icosahedral virus capsid by hierarchical assembly of subunits with designed asymmetry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhongchao Zhao ◽  
Joseph Che-Yen Wang ◽  
Mi Zhang ◽  
Nicholas A. Lyktey ◽  
Martin F. Jarrold ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Medical Applications ◽  
Virus Capsid ◽  
Viral Capsids ◽  
Hierarchical Assembly ◽  
Assembly Pathway ◽  
B Virus ◽  
Icosahedral Virus ◽  
Surface Chemistries ◽  
Virus Capsid Protein

AbstractSymmetrical protein complexes are ubiquitous in biology. Many have been re-engineered for chemical and medical applications. Viral capsids and their assembly are frequent platforms for these investigations. A means to create asymmetric capsids may expand applications. Here, starting with homodimeric Hepatitis B Virus capsid protein, we develop a heterodimer, design a hierarchical assembly pathway, and produce asymmetric capsids. In the heterodimer, the two halves have different growth potentials and assemble into hexamers. These preformed hexamers can nucleate co-assembly with other dimers, leading to Janus-like capsids with a small discrete hexamer patch. We can remove the patch specifically and observe asymmetric holey capsids by cryo-EM reconstruction. The resulting hole in the surface can be refilled with fluorescently labeled dimers to regenerate an intact capsid. In this study, we show how an asymmetric subunit can be used to generate an asymmetric particle, creating the potential for a capsid with different surface chemistries.

scholarly journals A Kinase Chaperones Hepatitis B Virus Capsid Assembly and Captures Capsid Dynamics in vitro

2011 ◽  
Vol 7 (11) ◽  
pp. e1002388 ◽  
Author(s):  
Chao Chen ◽  
Joseph Che-Yen Wang ◽  
Adam Zlotnick
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus

scholarly journals Dissecting the Fine Details of Assembly of aT = 3 Phage Capsid

2005 ◽  
Vol 6 (2) ◽  
pp. 119-125 ◽  
Author(s):  
P. G. Stockley ◽  
A. E. Ashcroft ◽  
S. Francese ◽  
G. S. Thompson ◽  
N. A. Ranson ◽  
...  
Keyword(s):  
Rna Binding ◽  
Protein Complexes ◽  
Model Systems ◽  
Replicase Gene ◽  
Nmr Studies ◽  
Partial Explanation ◽  
Stem Loop ◽  
Assembly Pathway

The RNA bacteriophages represent ideal model systems in which to probe the detailed assembly pathway for the formation of aT = 3 quasi-equivalent capsid. For MS2, the assembly reaction can be probedin vitrousing acid disassembled coat protein subunits and a short (19 nt) RNA stem-loop that acts as the translational operator of the replicase gene and leads to sequence-specific sequestration and packaging of the cognate phage RNAin vivo. Reassembly reactions can be initiated by mixing these components at neutral pH. The molecular basis of the sequence-specific RNA–protein interaction is now well understood. Recent NMR studies on the protein demonstrate extensive mobility in the loops of the polypeptide that alter their conformations to form the quasi-equivalent conformers of the final capsid. It seems reasonable to assume that RNA binding results in reduction of this flexibility. However, mass spectrometry suggests that these RNA–protein complexes may only provide one type of quasi-equivalent capsid building block competent to form five-fold axes but not the full shell. Work with longer RNAs suggests that the RNA may actively template the assembly pathway providing a partial explanation of how conformers are selected in the growing shell.

scholarly journals Nuclear Export and Import of Human Hepatitis B Virus Capsid Protein and Particles

2010 ◽  
Vol 6 (10) ◽  
pp. e1001162 ◽  
Author(s):  
Hung-Cheng Li ◽  
Er-Yi Huang ◽  
Pei-Yi Su ◽  
Szu-Yao Wu ◽  
Ching-Chun Yang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Protein ◽  
Nuclear Export ◽  
Virus Capsid ◽  
Human Hepatitis ◽  
B Virus ◽  
Virus Capsid Protein

scholarly journals Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

1999 ◽  
Vol 80 (5) ◽  
pp. 1253-1262 ◽  
Author(s):  
O Rosmorduc ◽  
H Sirma ◽  
P Soussan ◽  
E Gordien ◽  
P Lebon ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Protein Expression ◽  
Capsid Protein ◽  
Virus Capsid ◽  
B Virus ◽  
Virus Capsid Protein
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