Börger Claudia, Schünke Sven, Lecher Justin, Stoldt Matthias, Winkhaus Friederike, Kaupp U Benjamin, Willbold Dieter
Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich, 52425, Jülich, Germany.
Institut für Physikalische Biologie, Heinrich-Heine-Universität, 40225, Düsseldorf, Germany.
Biomol NMR Assign. 2015 Oct;9(2):243-6. doi: 10.1007/s12104-014-9583-x. Epub 2014 Oct 17.
Hyperpolarization activated and cyclic nucleotide-gated (HCN) ion channels as well as cyclic nucleotide-gated (CNG) ion channels are essential for the regulation of cardiac cells, neuronal excitability, and signaling in sensory cells. Both classes are composed of four subunits. Each subunit comprises a transmembrane region, intracellular N- and C-termini, and a C-terminal cyclic nucleotide-binding domain (CNBD). Binding of cyclic nucleotides to the CNBD promotes opening of both CNG and HCN channels. In case of CNG channels, binding of cyclic nucleotides to the CNBD is sufficient to open the channel. In contrast, HCN channels open upon membrane hyperpolarization and their activity is modulated by binding of cyclic nucleotides shifting the activation potential to more positive values. Although several high-resolution structures of CNBDs from HCN and CNG channels are available, the gating mechanism for murine HCN2 channel, which leads to the opening of the channel pore, is still poorly understood. As part of a structural investigation, here, we report the complete backbone and side chain resonance assignments of the murine HCN2 CNBD with part of the C-linker.
超极化激活的环核苷酸门控（HCN）离子通道以及环核苷酸门控（CNG）离子通道对于调节心脏细胞、神经元兴奋性和感觉细胞中的信号传导至关重要。这两类通道均由四个亚基组成。每个亚基都包含一个跨膜区域、细胞内的N端和C端，以及一个C端环核苷酸结合结构域（CNBD）。环核苷酸与CNBD的结合促进CNG和HCN通道的开放。对于CNG通道而言，环核苷酸与CNBD的结合足以打开通道。相比之下，HCN通道在膜超极化时开放，其活性通过环核苷酸的结合进行调节，使激活电位向更正的值移动。尽管已有来自HCN和CNG通道的几种CNBD的高分辨率结构，但导致小鼠HCN2通道孔开放的门控机制仍知之甚少。作为结构研究的一部分，在此我们报告了带有部分C连接子的小鼠HCN2 CNBD的完整主链和侧链共振归属。
