New View Emerges of Ion Channel Linked to Blindness

Columbia University Vagelos College of Physicians and Surgeon researchers have generated high resolution three-dimensional images of an ion channel that is essential for vision and smell in vertebrates.


Opening of the TAX-4 channel
Opening of the TAX-4 channel (Columbia University Irving Medical Center)


Cyclic nucleotide-gated (CNG) channels convert electromagnetic and chemical signals into electrical signals in the eye and nose, which are transmitted to and processed by the brain. Mutations in CNG channel genes are associated with degenerative visual disorders that cause blindness or color blindness.


The Findings

The researchers used cryo-electron microscopy to study the structure of TAX-4, a CNG channel found in roundworms that is related to the human variant. The resulting images of the structure reveal for the first time how the channel is activated: When cyclic nucleotide molecules bind to the outside of the channel, a double-barrier gate located 5 nanometers away in the central cavity opens.

Structure and mechanism of TAX-4 channel
Structure and mechanism of the TAX-4 channel (Credit: Columbia University Irving Medical Center)


The Bigger Picture

The images challenge a long-held theory in the ion channel field, which suggests that the activation gate is located at the external entrance of CNG channels, and provide a blueprint for mapping the locations of disease-causing mutations and elucidating how the mutations alter CNG channel structure and function.



More Information

The paper is published in Nature Structural & Molecular Biology and is titled “Mechanism of ligand activation of a eukaryotic cyclic nucleotide−gated channel.”


The Columbia University authors are Jian Yang, Joachim Frank, Xiangdong Zheng, Ziao Fu, Minghui Li, Huan Li, Shufang Li, Robert A. Grassucci, and Zhengshan Hu. The other authors are Deyuan Su, Yuebin Zhang, Yaping Pan, Zhenning Ren, Xueming Li, Ming Zhou, and Guohui Li.


The study was supported by grants from the National Institutes of Health (RO1EY027800 and RO1GM085234, RO1GM55440).

The authors declare no financial or other conflicts of interest.