Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen, Switzerland.
Department of Biology, ETH-Zurich, Zurich, Switzerland.
Nat Struct Mol Biol. 2022 Jan;29(1):32-39. doi: 10.1038/s41594-021-00700-8. Epub 2021 Dec 30.
In rod photoreceptors of the retina, the cyclic nucleotide-gated (CNG) channel is composed of three CNGA and one CNGB subunits, and it closes in response to light activation to generate an electrical signal that is conveyed to the brain. Here we report the cryo-EM structure of the closed state of the native rod CNG channel isolated from bovine retina. The structure reveals differences between CNGA1 and CNGB1 subunits. Three CNGA1 subunits are tethered at their C terminus by a coiled-coil region. The C-helix in the cyclic nucleotide-binding domain of CNGB1 features a different orientation from that in the three CNGA1 subunits. The arginine residue R994 of CNGB1 reaches into the ionic pathway and blocks the pore, thus introducing an additional gate, which is different from the central hydrophobic gate known from homomeric CNGA channels. These results address the long-standing question of how CNGB1 subunits contribute to the function of CNG channels in visual and olfactory neurons.
在视网膜的视杆细胞中，环核苷酸门控 (CNG) 通道由三个 CNGA 和一个 CNGB 亚基组成，它在光激活时关闭，产生电信号，传递到大脑。在这里，我们报告了从牛视网膜中分离出的天然视杆 CNG 通道的封闭状态的冷冻电镜结构。该结构揭示了 CNGA1 和 CNGB1 亚基之间的差异。三个 CNGA1 亚基通过卷曲螺旋区域在其 C 末端连接。CNGB1 环核苷酸结合域中的 C 螺旋的取向与三个 CNGA1 亚基中的不同。CNGB1 的精氨酸残基 R994 进入离子通道并阻塞孔，从而引入了一个额外的门，这与同源性 CNG 通道中已知的中央疏水性门不同。这些结果解决了长期以来的问题，即 CNGB1 亚基如何为视觉和嗅觉神经元中的 CNG 通道的功能做出贡献。
