气候变化领域集成服务门户(CCPortal): Molecular mechanism of capsid disassembly in hepatitis B virus

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DOI	10.1073/pnas.2102530118
	Molecular mechanism of capsid disassembly in hepatitis B virus
	Ghaemi Z.; Gruebele M.; Tajkhorshid E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:36
英文摘要	The disassembly of a viral capsid leading to the release of its genetic material into the host cell is a fundamental step in viral infection. In hepatitis B virus (HBV), the capsid consists of identical protein monomers that dimerize and then arrange themselves into pentamers or hexamers on the capsid surface. By applying atomistic molecular dynamics simulation to an entire solvated HBV capsid subjected to a uniform mechanical stress protocol, we monitor the capsid-disassembly process and analyze the process down to the level of individual amino acids in 20 independent simulation replicas. The strain of an isotropic external force, combined with structural fluctuations, causes structurally heterogeneous cracks to appear in the HBV capsid. Analysis of the monomer-monomer interfaces reveals that, in contrast to the expectation from purely mechanical considerations, the cracks mainly occur within hexameric sites, whereas pentameric sites remain largely intact. Only a small subset of the capsid protein monomers, different in each simulation, are engaged in each instance of disassembly. We identify specific residues whose interactions are most readily lost during disassembly; R127, I139, Y132, N136, A137, and V149 are among the hot spots at the interfaces between dimers that lie within hexamers, leading to disassembly. The majority of these hot-spot residues are conserved by evolution, hinting to their importance for disassembly by avoiding overstabilization of capsids. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atomistic molecular dynamics simulations; Capsid disassembly; Hepatitis B virus
语种	英语
scopus关键词	capsid protein; Article; carboxy terminal sequence; controlled study; Hepatitis B virus; mechanical stress; nonhuman; protein phosphorylation; virus assembly; virus capsid; virus characterization; virus morphology; virus strain
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238808
作者单位	Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; NIH Center for Macromolecular Modeling and Bionformatics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
推荐引用方式 GB/T 7714	Ghaemi Z.,Gruebele M.,Tajkhorshid E.. Molecular mechanism of capsid disassembly in hepatitis B virus[J],2021,118(36).
APA	Ghaemi Z.,Gruebele M.,&Tajkhorshid E..(2021).Molecular mechanism of capsid disassembly in hepatitis B virus.Proceedings of the National Academy of Sciences of the United States of America,118(36).
MLA	Ghaemi Z.,et al."Molecular mechanism of capsid disassembly in hepatitis B virus".Proceedings of the National Academy of Sciences of the United States of America 118.36(2021).