Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels | |
Lv SQ(吕守芹); An HL; Zhang HL; Long M(龙勉); Long, M (reprint author), Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China. | |
发表期刊 | MOLECULAR NEUROBIOLOGY |
2016 | |
卷号 | 53期号:9页码:5948-5961 |
ISSN | 0893-7648 |
摘要 | The effect of the conserved Leu/Ile site in the CD loop on the gating dynamics of Kir channels and corresponding micro-structural mechanism remains unclear. Molecular dynamics simulations were performed to investigate the structural mechanism of chicken Kir2.2. Compared to WT, the I223L mutant channel bound to PIP2 more strongly, was activated more rapidly, and maintained the activation state more stably after PIP2 dissociation. Cellular electrophysiology assays of mouse Kir2.1 and human Kir2.2 indicated that, consistent with simulations, the Leu residue increased the channel responses to PIP2 through increased binding affinity and faster activation kinetics, and the deactivation kinetics decreased upon PIP2 inhibition. The Ile residue induced the opposite responses. This difference was attributed to the distinct hydrophobic side chain symmetries of Leu and Ile; switching between these residues caused the interaction network to redistribute and offered effective conformation transduction in the Leu systems, which had more rigid and independent subunits. |
关键词 | Inward-rectifier Potassiumchannel Molecular Dynamicssimulations Conformationalchange Patchclamp Structure-function Relationship |
DOI | 10.1007/s12035-015-9466-x |
URL | 查看原文 |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000387231300012 |
关键词[WOS] | Inward-rectifier potassiumchannel ; Molecular dynamicssimulations ; Conformationalchange ; Patchclamp ; Structure-function relationship |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
项目资助者 | MD simulations were performed at the Supercomputing Center of the Chinese Academy of Sciences (CAS) and at the National Supercomputer Center in Tianjin. This work was supported by National Natural Science Foundation of China grants 31230027, 11342002, 11372332,11247010, and 11475053, National Key Basic Research Foundation of China grant 2011CB710904, CAS Knowledge Innovation Program grant KJCX2-YW-L08, and Natural Science Foundation for Distinguished Young Scholars of the Hebei Province of China grant C2015202340. |
课题组名称 | NML分子-细胞生物力学与空间生命科学 |
论文分区 | 一类 |
力学所作者排名 | True |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://dspace.imech.ac.cn/handle/311007/59686 |
专题 | 微重力重点实验室 |
通讯作者 | Long, M (reprint author), Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China. |
推荐引用方式 GB/T 7714 | Lv SQ,An HL,Zhang HL,et al. Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels[J]. MOLECULAR NEUROBIOLOGY,2016,53,9,:5948-5961. |
APA | Lv SQ,An HL,Zhang HL,Long M,&Long, M .(2016).Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels.MOLECULAR NEUROBIOLOGY,53(9),5948-5961. |
MLA | Lv SQ,et al."Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels".MOLECULAR NEUROBIOLOGY 53.9(2016):5948-5961. |
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