Mapping of the Physical Interaction between the Intracellular Domains of an Inwardly Rectifying Potassium Channel, Kir6.2*

Mapping of the Physical Interaction between the Intracellular Domains of an Inwardly Rectifying Potassium Channel, Kir6.2*
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内向整流钾通道的细胞内域之间的物理相互作用图谱,Kir6.2*

DOI:
10.1074/jbc.274.47.33393
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发表时间:
1999
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
F. Ashcroft
F. Ashcroft
中科院分区:
--
文献类型:
--
作者:
S. Tucker;F. Ashcroft

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内向整流钾(KIR)通道亚基的氨基末端和羧基末端都位于细胞内。越来越多的证据表明,这两个结构域都是G蛋白和核苷酸等药物调节KIR通道所必需的。Kir6.2是ATP敏感K+(K-ATP)通道的致孔亚单位。利用体外蛋白质-蛋白质相互作用分析,我们证明了Kir6.2的两个胞内结构域相互作用,并在N端定位了负责这种相互作用的区域。通过这种相互作用的“串扰”可以解释N或C末端的突变如何影响Kir6.2的内在ATP敏感性。有趣的是,“相互作用结构域”在整个KIR通道超家族中高度保守。Kir6.2的N-末端相互作用结构域也可以与Kir6.1和Kir2.1的C末端相互作用。此外,N端相互作用结构域保守区内的突变破坏了它与C末端的相互作用,严重损害了Kir6.2和Kir2.1形成功能通道的能力,这表明这种相互作用可能是KIR钾通道家族所有成员的共同特征。
The amino-terminal and carboxyl-terminal domains of inwardly rectifying potassium (Kir) channel subunits are both intracellular. There is increasing evidence that both of these domains are required for the regulation of Kir channels by agents such as G-proteins and nucleotides. Kir6.2 is the pore-forming subunit of the ATP-sensitive K+ (K ATP) channel. Using an in vitro protein-protein interaction assay, we demonstrate that the two intracellular domains of Kir6.2 physically interact with each other, and we map a region within the N terminus that is responsible for this interaction. “Cross-talk” through this interaction may explain how mutations in either the N or C terminus can influence the intrinsic ATP-sensitivity of Kir6.2. Interestingly, the “interaction domain” is highly conserved throughout the superfamily of Kir channels. The N-terminal interaction domain of Kir6.2 can also interact with the C terminus of both Kir6.1 and Kir2.1. Furthermore, a mutation within the conserved region of the N-terminal interaction domain, which disrupts its interaction with the C terminus, severely compromised the ability of both Kir6.2 and Kir2.1 to form functional channels, suggesting that this interaction may be a feature common to all members of the Kir family of potassium channels.
ROMK1 (Kir 1.1a) 内向整流 K 通道亚基的组装涉及多个相互作用位点。
DOI: 10.1016/s0006-3495(98)77892-0
发表时间: 1998
期刊: Biophysical journal.
影响因子: --
作者:
Koster,JC;Bentle,KA;Nichols,CG;Ho,K
通讯作者: Ho,K