Roosild Tarmo P, Castronovo Samantha, Miller Samantha, Li Chan, Rasmussen Tim, Bartlett Wendy, Gunasekera Banuri, Choe Senyon, Booth Ian R
Drug Development Department, Nevada Cancer Institute, Las Vegas, NV 89135, USA.
Structure. 2009 Jun 10;17(6):893-903. doi: 10.1016/j.str.2009.03.018.
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.
KTN（RCK）结构域是核苷酸结合折叠结构，可形成各种钾离子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孔形成对应物的机制仍不清楚。KTN（RCK）结构域在不对称单元内始终以二聚体形式结晶，在两个罗斯曼折叠之间形成明显的铰链。我们之前曾提出，铰链角的改变在激活通道或转运蛋白的相关膜整合成分中起重要作用。在此，我们报告了大肠杆菌KefC钾离子外流系统的含KTN的C末端结构域与辅助亚基KefF结合的结构，已知KefF可稳定传导状态。复合物的结构以及KefC变体的功能分析表明，KTN二聚体铰链固有的构象灵活性受KefF调节，并且对KefC离子通量的调节至关重要。
