气候变化领域集成服务门户(CCPortal): Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill

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DOI	10.1073/pnas.1805442115
	Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill
	Lin X.; Noel J.K.; Wang Q.; Ma J.; Onuchic J.N.
发表日期	2018
ISSN	0027-8424
起始页码	E7905
结束页码	E7913
卷号	115 期号:34
英文摘要	Influenza hemagglutinin (HA) mediates viral entry into host cells through a large-scale conformational rearrangement at low pH that leads to fusion of the viral and endosomal membranes. Crystallographic and biochemical data suggest that a loop-to-coiled-coil transition of the B-loop region of HA is important for driving this structural rearrangement. However, the microscopic picture for this proposed “spring-loaded” movement is missing. In this study, we focus on understanding the transition of the B loop and perform a set of all-atom molecular dynamics simulations of the full B-loop trimeric structure with the CHARMM36 force field. The free-energy profile constructed from our simulations describes a B loop that stably folds half of the postfusion coiled coil in tens of microseconds, but the full coiled coil is unfavorable. A buried hydrophilic residue, Thr59, is implicated in destabilizing the coiled coil. Interestingly, this conserved threonine is the only residue in the B loop that strictly differentiates between the group 1 and 2 HA molecules. Microsecond-scale constant temperature simulations revealed that kinetic traps in the structural switch of the B loop can be caused by nonnative, intra-monomer, or intermonomer β-sheets. The addition of the A helix stabilized the postfusion state of the B loop, but introduced the possibility for further β-sheet structures. Overall, our results do not support a description of the B loop in group 2 HAs as a stiff spring, but, rather, it allows for more structural heterogeneity in the placement of the fusion peptides during the fusion process. © 2018 National Academy of Sciences. All Rights Reserved.
英文关键词	All-atom molecular dynamics; B-loop transition; Buried water; Sequence divergence; Structural heterogeneity
语种	英语
scopus关键词	Influenza virus hemagglutinin; threonine; Influenza virus hemagglutinin; alpha helix; amino terminal sequence; Article; B loop; beta sheet; carboxy terminal sequence; conformational transition; controlled study; crystal structure; hydrogen bond; hydrophobicity; loop to coiled coil transition; molecular dynamics; molecular interaction; molecular stability; pH; priority journal; protein folding; protein modification; protein refolding; protein structure; residue analysis; sequence analysis; structure activity relation; structure analysis; thermodynamics; chemistry; Influenza A virus; metabolism; protein quaternary structure; protein secondary structure; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A virus; Molecular Dynamics Simulation; Protein Structure, Quaternary; Protein Structure, Secondary
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/160477
作者单位	Lin, X., Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, United States, Department of Physics and Astronomy, Rice University, Houston, TX 77005, United States; Noel, J.K., Crystallography, Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany; Wang, Q., Verna and Marrs McLean Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States; Ma, J., Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, United States, Verna and Marrs McLean Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States, Department of Bioengineering, Rice University, Houston, TX 77030, United States; Onuchic, J.N., Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, United States, Department of Physics and Astronomy, Rice University, Houston, TX 77005, United States, Department ofChemistry, Rice University, Houston, TX 77005, United St...
推荐引用方式 GB/T 7714	Lin X.,Noel J.K.,Wang Q.,et al. Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill[J],2018,115(34).
APA	Lin X.,Noel J.K.,Wang Q.,Ma J.,&Onuchic J.N..(2018).Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill.Proceedings of the National Academy of Sciences of the United States of America,115(34).
MLA	Lin X.,et al."Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill".Proceedings of the National Academy of Sciences of the United States of America 115.34(2018).