气候变化领域集成服务门户(CCPortal): Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation

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DOI	10.1073/pnas.2024928118
	Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation
	Pajak J.; Atz R.; Hilbert B.J.; Morais M.C.; Kelch B.A.; Jardine P.J.; Arya G.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Many viruses utilize ringed packaging ATPases to translocate double-stranded DNA into procapsids during replication. A critical step in the mechanochemical cycle of such ATPases is ATP binding, which causes a subunit within the motor to grip DNA tightly. Here, we probe the underlying molecular mechanism by which ATP binding is coupled to DNA gripping and show that a glutamate-switch residue found in AAA+ enzymes is central to this coupling in viral packaging ATPases. Using free-energy landscapes computed through molecular dynamics simulations, we determined the stable conformational state of the ATPase active site in ATP- and ADP-bound states. Our results show that the catalytic glutamate residue transitions from an active to an inactive pose upon ATP hydrolysis and that a residue assigned as the glutamate switch is necessary for regulating this transition. Furthermore, we identified via mutual information analyses the intramolecular signaling pathway mediated by the glutamate switch that is responsible for coupling ATP binding to conformational transitions of DNA-gripping motifs. We corroborated these predictions with both structural and functional experimental measurements. Specifically, we showed that the crystal structure of the ADP-bound P74-26 packaging ATPase is consistent with the structural coupling predicted from simulations, and we further showed that disrupting the predicted signaling pathway indeed decouples ATPase activity from DNA translocation activity in the φ29 DNA packaging motor. Our work thus establishes a signaling pathway that couples chemical and mechanical events in viral DNA packaging motors. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Allosteric coupling; ATPase; Bacteriophage; DNA packaging; Molecular motor
语种	英语
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/179747
作者单位	Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, United States; Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN 55455, United States; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, United States; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550, United States
推荐引用方式 GB/T 7714	Pajak J.,Atz R.,Hilbert B.J.,et al. Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation[J],2021,118(17).
APA	Pajak J..,Atz R..,Hilbert B.J..,Morais M.C..,Kelch B.A..,...&Arya G..(2021).Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Pajak J.,et al."Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).