Identification of the Conformational transition pathway in PIP2 Opening Kir Channels

	Identification of the Conformational transition pathway in PIP2 Opening Kir Channels
	Li JW; Lv SQ(吕守琴); Liu YZ; Pang CL; Chen YF; Zhang SH; Yu H; Long M(龙勉); Zhang HL; Logothetis DE
刊名	SCIENTIFIC REPORTS
	2015-06-11
通讯作者邮箱	zhany@hebut.edu.cn ; hailong_an@hebut.edu.cn
卷号	5 页码:11289
ISSN号	2045-2322
通讯作者	An, HL (reprint author), Hebei Univ Technol, Inst Biophys, Sch Sci, Key Lab Mol Biophys, Tianjin 300401, Hebei Province, Peoples R China.
产权排序	[Li, Junwei; Pang, Chunli; Chen, Yafei; Zhang, Suhua; Yu, Hui; Zhan, Yong; An, Hailong] Hebei Univ Technol, Inst Biophys, Sch Sci, Key Lab Mol Biophys, Tianjin 300401, Hebei Province, Peoples R China; [Lu, Shouqin; Long, Mian] Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China; [Lu, Shouqin; Long, Mian] Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Key Lab Micrograv, Beijing 100190, Peoples R China; [Liu, Yuzhi] Shijiazhuang Tiedao Univ, Sch Elect & Elect Engn, Shijiazhuang 050043, Peoples R China; [Zhang, Hailin] Hebei Med Univ, Dept Pharmacol, Key Lab Pharmacol & Toxicol New Drug, Minist Educ,Key Lab Neural & Vasc Biol, Shijiazhuang 050017, Hebei Province, Peoples R China; [Logothetis, Diomedes E.] Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23298 USA
中文摘要	The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2 regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2.
分类号	一类
类目[WOS]	Multidisciplinary Sciences
研究领域[WOS]	Science & Technology - Other Topics
收录类别	SCI
原文出处	http://dx.doi.org/10.1038/srep11289
语种	英语
WOS记录号	WOS:000356099300001
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/54972]
专题	力学研究所_国家微重力实验室
推荐引用方式 GB/T 7714	Li JW,Lv SQ,Liu YZ,et al. Identification of the Conformational transition pathway in PIP2 Opening Kir Channels[J]. SCIENTIFIC REPORTS,2015,5:11289.
APA	Li JW.,Lv SQ.,Liu YZ.,Pang CL.,Chen YF.,...&An HL.(2015).Identification of the Conformational transition pathway in PIP2 Opening Kir Channels.SCIENTIFIC REPORTS,5,11289.
MLA	Li JW,et al."Identification of the Conformational transition pathway in PIP2 Opening Kir Channels".SCIENTIFIC REPORTS 5(2015):11289.