气候变化领域集成服务门户(CCPortal): A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6

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DOI	10.1073/pnas.2016730118
	A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6
	McGrath K.; Agarwal S.; Tonelli M.; Dergai M.; Gaeta A.L.; Shum A.K.; Lacoste J.; Zhang Y.; Wen W.; Chung D.; Wiersum G.; Shevade A.; Zaichick S.; van Rossum D.B.; Shuvalova L.; Savas J.N.; Kuchin S.; Taipale M.; Caldwell K.A.; Caldwell G.A.; Fasshauer D.; Caraveo G.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Ykt6 is a soluble N-ethylmaleimide sensitive factor activating protein receptor (SNARE) critically involved in diverse vesicular fusion pathways. While most SNAREs rely on transmembrane domains for their activity, Ykt6 dynamically cycles between the cytosol and membrane-bound compartments where it is active. The mechanism that regulates these transitions and allows Ykt6 to achieve specificity toward vesicular pathways is unknown. Using a Parkinson’s disease (PD) model, we found that Ykt6 is phosphorylated at an evolutionarily conserved site which is regulated by Ca2+ signaling. Through a multidisciplinary approach, we show that phosphorylation triggers a conformational change that allows Ykt6 to switch from a closed cytosolic to an open membrane-bound form. In the phosphorylated open form, the spectrum of protein interactions changes, leading to defects in both the secretory and autophagy pathways, enhancing toxicity in PD models. Our studies reveal a mechanism by which Ykt6 conformation and activity are regulated with potential implications for PD. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	SNARE \| calcineurin \| Parkinson’s disease \| conformation \| Ykt6
语种	英语
scopus关键词	alpha synuclein; calcineurin; SNARE protein; SNARE protein Ykt6; unclassified drug; Article; autophagy (cellular); binding affinity; calcium signaling; cellular distribution; conformational transition; controlled study; cytosol; embryo; genetic conservation; human; human cell; neuropathology; nonhuman; Parkinson disease; priority journal; protein domain; protein interaction; protein phosphorylation; secretory pathway
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/180130
作者单位	Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; National Magnetic Resonance Facility at Madison, University of Wisconsin, Madison, WI 53706, United States; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland; Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35401, United States; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Integrated Molecular Structure Education and Research Center, Department of Chemistry, Northwestern University, Evanston, IL 60208, United States; Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Center for Structural Genomics of Infectious Diseases, Northwestern University, Chicago, IL 60611, United States; Department of Biological Sciences, University of Wisconsin, Milwaukee, WI 53211, United States; Division of Experimental Pathology, Department o...
推荐引用方式 GB/T 7714	McGrath K.,Agarwal S.,Tonelli M.,et al. A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6[J],2021,118(12).
APA	McGrath K..,Agarwal S..,Tonelli M..,Dergai M..,Gaeta A.L..,...&Caraveo G..(2021).A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	McGrath K.,et al."A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).