SUR-dependent Modulation of KATP Channels by an N-terminal KIR6.2 Peptide
SUR-dependent Modulation of KATP Channels by an N-terminal KIR6.2 Peptide
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N 端 KIR6.2 肽对 KATP 通道的 SUR 依赖性调节
DOI：
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发表时间：
2002
影响因子：
4.8
通讯作者：
J. Bryan
中科院分区：
文献类型：
--
作者：
A. P. Babenko;J. Bryan
Ntp和Ctp分别是基于KIR6.0的N端和C端序列的合成肽，用于探测KIR6.0/SUR KATP通道的门控。微摩尔Ntp剂量依赖性地增加无配体溶液中的平均开放通道概率（PO（max）），减弱ATP对KIR6.2/SUR 1的抑制，但对同源KIR6.2通道无影响。Ntp（高达10−4 m）对平均开放或“快速”、K+驱动力依赖的爆发内闭合时间没有显著影响，证实了Ntp选择性地调节平均爆发与爆发间时间的比率。Ctp和Rnp，一个随机化的Ntp，没有影响，表明Ntp的影响是结构特异性的。Ntp打开KIR6.1/SUR 1通道，通常在缺乏刺激性Mg−核苷酸的情况下沉默，并减弱高亲和力磺酰脲结合与KATP孔闭合的偶联。这些效应与KIR6.0的N端缺失（ΔN）类似，在无Mg ~（2+）存在下，Ntp作用于ΔNKATP通道可降低其PO（max）和ATP的表观IC_（50）。结果是一致的竞争之间的NTP和内源性N末端的相互作用的网站上的细胞质面的通道或与删除的N末端NTP，分别与部分替换。已知SUR 1的KIR N端和TMD 0-L0片段控制PO（max）。据报道，L0接头是格列本脲结合所必需的，ΔNKIR6.2/SUR 1通道显示125 I-叠氮格列本脲标记KIR的减少，这意味着KIR N末端和SUR 1的L0接近。我们假设L0在配体抑制的KATP通道中与KIR N末端相互作用，并提出了一个模型，该模型基于BtuCD、MsbA和KcsA通道的结构，其中TMD 0-L0将SUR的MDR样核心与KIR孔连接。
Ntp and Ctp, synthetic peptides based on the N- and C-terminal sequences of KIR6.0, respectively, were used to probe gating of KIR6.0/SUR KATPchannels. Micromolar Ntp dose-dependently increased the mean open channel probability in ligand-free solution (P O(max)) and attenuated the ATP inhibition of KIR6.2/SUR1, but had no effect on homomeric KIR6.2 channels. Ntp (up to ∼10−4 m) did not affect significantly the mean open or “fast,” K+ driving force-dependent, intraburst closed times, verifying that Ntp selectively modulates the ratio of mean burst to interburst times. Ctp and Rnp, a randomized Ntp, had no effect, indicating that the effects of Ntp are structure specific. Ntp opened KIR6.1/SUR1 channels normally silent in the absence of stimulatory Mg− nucleotide(s) and attenuated the coupling of high-affinity sulfonylurea binding with KATP pore closure. These effects resemble those seen with N-terminal deletions (ΔN) of KIR6.0, and application of Ntp to ΔNKATP channels decreased theirP O(max) and apparent IC50 for ATP in the absence of Mg2+. The results are consistent with a competition between Ntp and the endogenous N terminus for a site of interaction on the cytoplasmic face of the channel or with partial replacement of the deleted N terminus by Ntp, respectively. The KIR N terminus and the TMD0-L0 segment of SUR1 are known to control the P O(max). The L0 linker has been reported to be required for glibenclamide binding, and ΔNKIR6.2/SUR1 channels exhibit reduced labeling of KIR with 125I-azidoglibenclamide, implying that the KIR N terminus and L0 of SUR1 are in proximity. We hypothesize that L0 interacts with the KIR N terminus in ligand-inhibited KATP channels and put forward a model, based on the architecture of BtuCD, MsbA, and the KcsA channel, in which TMD0-L0 links the MDR-like core of SUR with the KIR pore.
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影响因子：
--
作者：
GILLIS, KD;GEE, WM;MISLER, S
通讯作者：
MISLER, S
影响因子：
56.9
作者：
Shyng, SL;Nichols, CG
通讯作者：
Nichols, CG
影响因子：
56.9
作者：
Gulbis, JM;Zhou, M;MacKinnon, R
通讯作者：
MacKinnon, R
k(ir)6.2 的 I182 区域与 ATP 抑制 K(ATP) 通道中的配体结合密切相关。
影响因子：
3.4
作者：
Li,L;Wang,J;Drain,P
通讯作者：
Drain,P