Department of Biological Sciences, Columbia University, New York, NY, USA.
Nat Struct Mol Biol. 2022 Jan;29(1):40-46. doi: 10.1038/s41594-021-00699-y. Epub 2021 Dec 30.
Cyclic nucleotide-gated (CNG) channels transduce light-induced chemical signals into electrical signals in retinal cone and rod photoreceptors. Structures of native CNG channels, which are heterotetramers formed by CNGA and CNGB subunits, have not been obtained. In the present study, we report a high-resolution cryo-electron microscopy structure of the human cone CNG channel in the apo closed state. The channel contains three CNGA3 and one CNGB3 subunits. Arg403 in the pore helix of CNGB3 projects into an asymmetric selectivity filter and forms hydrogen bonds with two pore-lining backbone carbonyl oxygens. Arg442 in S6 of CNGB3 protrudes into and occludes the pore below the hydrophobic cavity gate previously observed in homotetrameric CNGA channels. It is interesting that Arg403Gln is a disease mutation, and Arg442 is replaced by glutamine in some animal species with dichromatic or monochromatic vision. These and other unique structural features and the disease link conferred by CNGB3 indicate a critical role of CNGB3 in shaping cone photoresponses.
环核苷酸门控 (CNG) 通道将光诱导的化学信号转导为视网膜视锥和视杆光感受器中的电信号。尚未获得由 CNGA 和 CNGB 亚基组成的异四聚体的天然 CNG 通道结构。在本研究中，我们报告了人锥体 CNG 通道在apo 关闭状态下的高分辨率冷冻电镜结构。该通道包含三个 CNGA3 和一个 CNGB3 亚基。CNGB3 孔螺旋中的 Arg403 突入非对称选择性过滤器，并与两个孔衬里骨架羰基氧形成氢键。CNGB3 的 S6 中的 Arg442 突出并阻塞先前在同三聚体 CNGA 通道中观察到的疏水腔门下方的孔。有趣的是，Arg403Gln 是一种疾病突变，而 Arg442 在具有双色或单色视觉的某些动物物种中被谷氨酰胺取代。这些和其他独特的结构特征以及由 CNGB3 赋予的疾病联系表明，CNGB3 在塑造锥体光反应中起着关键作用。
