气候变化领域集成服务门户(CCPortal): Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel

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DOI	10.1073/pnas.2017280118
	Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel
	Chen H.; Deng J.; Cui Q.; Chanda B.; Henzler-Wildman K.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Temperature-dependent regulation of ion channel activity is critical for a variety of physiological processes ranging from immune response to perception of noxious stimuli. Our understanding of the structural mechanisms that underlie temperature sensing remains limited, in part due to the difficulty of combining high-resolution structural analysis with temperature stimulus. Here, we use NMR to compare the temperature-dependent behavior of Shaker potassium channel voltage sensor domain (WT-VSD) to its engineered temperature sensitive (TS-VSD) variant. Further insight into the molecular basis for temperature-dependent behavior is obtained by analyzing the experimental results together with molecular dynamics simulations. Our studies reveal that the overall secondary structure of the engineered TS-VSD is identical to the wild-type channels except for local changes in backbone torsion angles near the site of substitution (V369S and F370S). Remarkably however, these structural differences result in increased hydration of the voltage-sensing arginines and the S4-S5 linker helix in the TS-VSD at higher temperatures, in contrast to the WT-VSD. These findings highlight how subtle differences in the primary structure can result in large-scale changes in solvation and thereby confer increased temperaturedependent activity beyond that predicted by linear summation of solvation energies of individual substituents. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Ion channels; MD; Thermosensing NMR; Voltage sensor domain
语种	英语
scopus关键词	arginine; Shaker potassium channel; Article; channel gating; conformational transition; controlled study; heating; high temperature; hydration; molecular dynamics; molecular mechanics; nuclear magnetic resonance spectroscopy; priority journal; protein domain; protein engineering; protein secondary structure; protein structure; solvation; temperature dependence; temperature sensitivity; torsion; wild type
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/180017
作者单位	Graduate Program in Biophysics, University of Wisconsin-Madison, Madison, WI 53706, United States; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States; Department of Chemistry, Boston University, Boston, MA 02215, United States; Department of Anesthesiology, Center for Investigation of Membrane Excitability Diseases, Washington University, School of Medicine, St. Louis, MO 63110, United States
推荐引用方式 GB/T 7714	Chen H.,Deng J.,Cui Q.,et al. Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel[J],2021,118(14).
APA	Chen H.,Deng J.,Cui Q.,Chanda B.,&Henzler-Wildman K..(2021).Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Chen H.,et al."Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).