气候变化领域集成服务门户(CCPortal): The structure of the native cardiac thin filament at systolic Ca2+ levels

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DOI	10.1073/pnas.2024288118
	The structure of the native cardiac thin filament at systolic Ca2+ levels
	Risi C.M.; Pepper I.; Belknap B.; Landim-Vieira M.; White H.D.; Dryden K.; Pinto J.R.; Chase P.B.; Galkin V.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Every heartbeat relies on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca2+ levels. Thin filaments are comprised of two actin strands, each harboring equally separated troponin complexes, which bind Ca2+ to move tropomyosin cables away from the myosin binding sites and, thus, activate systolic contraction. Recently, structures of thin filaments obtained at low (pCa ∼9) or high (pCa ∼3) Ca2+ levels revealed the transition between the Ca2+-free and Ca2+-bound states. However, in working cardiac muscle, Ca2+ levels fluctuate at intermediate values between pCa ∼6 and pCa ∼7. The structure of the thin filament at physiological Ca2+ levels is unknown. We used cryoelectron microscopy and statistical analysis to reveal the structure of the cardiac thin filament at systolic pCa = 5.8. We show that the two strands of the thin filament consist of a mixture of regulatory units, which are composed of Ca2+-free, Ca2+-bound, or mixed (e.g., Ca2+ free on one side and Ca2+ bound on the other side) troponin complexes. We traced troponin complex conformations along and across individual thin filaments to directly determine the structural composition of the cardiac native thin filament at systolic Ca2+ levels. We demonstrate that the two thin filament strands are activated stochastically with short-range cooperativity evident only on one of the two strands. Our findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cardiac regulation; Cryoelectron microscopy; Muscle contraction; Thin filament; Troponin complex
语种	英语
scopus关键词	troponin; Article; calcium cell level; cardiac muscle; cardiovascular autoregulation; cell composition; cell structure; controlled study; cryoelectron microscopy; human; human cell; muscle contraction; priority journal; protein conformation; statistical analysis; stochastic model; systole; thin filament
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/180057
作者单位	Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, United States; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32304, United States; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22903, United States; Department of Biological Science, Florida State University, Tallahassee, FL 32306, United States
推荐引用方式 GB/T 7714	Risi C.M.,Pepper I.,Belknap B.,et al. The structure of the native cardiac thin filament at systolic Ca2+ levels[J],2021,118(13).
APA	Risi C.M..,Pepper I..,Belknap B..,Landim-Vieira M..,White H.D..,...&Galkin V.E..(2021).The structure of the native cardiac thin filament at systolic Ca2+ levels.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Risi C.M.,et al."The structure of the native cardiac thin filament at systolic Ca2+ levels".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).