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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.
Source PublicationMOLECULAR NEUROBIOLOGY
2016
Volume53Issue:9Pages:5948-5961
ISSN0893-7648
Abstract

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.

KeywordInward-rectifier Potassiumchannel Molecular Dynamicssimulations Conformationalchange Patchclamp Structure-function Relationship
DOI10.1007/s12035-015-9466-x
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000387231300012
WOS KeywordInward-rectifier potassiumchannel ; Molecular dynamicssimulations ; Conformationalchange ; Patchclamp ; Structure-function relationship
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
Funding OrganizationMD 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.
DepartmentNML分子-细胞生物力学与空间生命科学
Classification一类
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Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/59686
Collection国家微重力实验室
Corresponding AuthorLong, M (reprint author), Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China.
Recommended Citation
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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