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DOI	10.1073/pnas.1914188117
	Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms
	Pabis A.; Rawle R.J.; Kasson P.M.
发表日期	2020
ISSN	0027-8424
起始页码	7200
结束页码	7207
卷号	117 期号:13
英文摘要	Enveloped viruses enter cells via a process of membrane fusion between the viral envelope and a cellular membrane. For influenza virus, mutational data have shown that the membraneinserted portions of the hemagglutinin protein play a critical role in achieving fusion. In contrast to the relatively well-understood ectodomain, a predictive mechanistic understanding of the intramembrane mechanisms by which influenza hemagglutinin drives fusion has been elusive. We used molecular dynamics simulations of fusion between a full-length hemagglutinin proteoliposome and a lipid bilayer to analyze these mechanisms. In our simulations, hemagglutinin first acts within the membrane to increase lipid tail protrusion and promote stalk formation and then acts to engage the distal leaflets of each membrane and promote stalk widening, curvature, and eventual fusion. These two sequential mechanisms, one occurring before stalk formation and one after, are consistent with our experimental measurements of single-virus fusion kinetics to liposomes of different sizes. The resulting model also helps explain and integrate previous mutational and biophysical data, particularly the mutational sensitivity of the fusion peptide N terminus and the length sensitivity of the transmembrane domain. We hypothesize that entry by other enveloped viruses may also use sequential processes of acyl tail exposure, followed by membrane curvature and distal leaflet engagement. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Influenza hemagglutinin; Molecular dynamics simulation; Viral membrane fusion
语种	英语
scopus关键词	fusion protein; Influenza virus hemagglutinin; liposome; proteoliposome; virus hemagglutinin; amino terminal sequence; Article; cell membrane; controlled study; kinetics; lipid bilayer; membrane fusion; membrane structure; molecular dynamics; nonhuman; prediction; priority journal; protein domain; protein function; protein structure; single virus fusion kinetics; virus entry; virus envelope; biological model; Orthomyxoviridae; physiology; Hemagglutinins, Viral; Models, Biological; Molecular Dynamics Simulation; Orthomyxoviridae; Virus Internalization
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/160303
作者单位	Pabis, A., Department of Cell and Molecular Biology, Uppsala University, Uppsala, 752 36, Sweden; Rawle, R.J., Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, United States, Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, United States, Department of Chemistry, Williams College, Williamstown, MA 01267, United States; Kasson, P.M., Department of Cell and Molecular Biology, Uppsala University, Uppsala, 752 36, Sweden, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, United States, Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, United States
推荐引用方式 GB/T 7714	Pabis A.,Rawle R.J.,Kasson P.M.. Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms[J],2020,117(13).
APA	Pabis A.,Rawle R.J.,&Kasson P.M..(2020).Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms.Proceedings of the National Academy of Sciences of the United States of America,117(13).
MLA	Pabis A.,et al."Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms".Proceedings of the National Academy of Sciences of the United States of America 117.13(2020).