KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation.

KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation.
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DOI:
10.1016/j.str.2009.03.018
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发表时间:
2009-06-10
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Booth IR
Booth IR
中科院分区:
其他
文献类型:
--
作者:
Roosild TP;Castronovo S;Miller S;Li C;Rasmussen T;Bartlett W;Gunasekera B;Choe S;Booth IR

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KTN (RCK) 结构域是核苷酸结合折叠,形成各种 K+ 通道和转运蛋白的细胞质调节复合物。尽管进行了大量的电生理学和结构研究,但这些蛋白质用于控制其跨膜成孔对应物的机制仍不清楚。 KTN (RCK) 结构域始终在不对称单元内结晶为二聚体,在两个罗斯曼折叠之间形成明显的铰链。我们之前提出,铰链角度的修改在激活通道或转运蛋白的相关膜集成组件中起着重要作用。在这里,我们报告了大肠杆菌 KefC K+ 外排系统的 C 端、KTN 承载结构域与辅助亚基 KefF 的结构,已知 KefF 可以稳定导电状态。 KefC 变体的复杂结构和功能分析表明,KTN 二聚体铰链固有的构象灵活性的控制受 KefF 调节,并且对于 KefC 离子通量的调节至关重要。
KTN (RCK) domains are nucleotide-binding folds that form the cytoplasmic regulatory complexes of various K+ channels and transporters. The mechanisms these proteins use to control their transmembrane pore-forming counterparts remains unclear despite numerous electrophysiological and structural studies. KTN (RCK) domains consistently crystallize as dimers within the asymmetric unit, forming a pronounced hinge between two Rossmann folds. We have previously proposed that modification of the hinge angle plays an important role in activating the associated membrane-integrated components of the channel or transporter. Here we report the structure of the C-terminal, KTN-bearing domain of the E. coli KefC K+ efflux system in association with the ancillary subunit, KefF, which is known to stabilize the conductive state. The structure of the complex and functional analysis of KefC variants reveal that control of the conformational flexibility inherent in the KTN dimer hinge is modulated by KefF and essential for regulation of KefC ion flux.
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