Structure of CNG Ion Channels in the Bovine Retina

Article: More insight into how vision works
Source: Paul Scherrer Institute (Switzerland)
Published: January 3, 2022

Light transduction in the rod photoreceptors of the retina occur by way of cyclic nucleotide-gated (CNG) ion channels, a gatekeeper ion channel that controls whether specific particles are allowed through the cell membrane into the interior of the receptor cell. In darkness, the ion channel is open, while in light the ion channel is triggered to close through a cascade of events. However, if the ion channel is not closed completely, the photoreceptor fails to prevent positively charged ions (such as calcium ions) from entering the cell, which in turn disrupts both the cell's electrochemical balance and the propagation of the hyperpolarization signal from the eye to the brain. In the present study, the researchers extracted the channel proteins from bovine eyes, a complex process that took two years to obtain enough protein to work with. The team then used cryo-electron microscopy to reveal the three-dimensional structure of the ion channel. PhD student and first author of the study explains, "In contrast to previous studies on the structure of the ion channel, we investigated the native protein as it exists in the eye. We are therefore much closer to the real conditions that exist in living creatures." The microscopy revealed that the protein comprises four parts: three lots of subunit A, and one lot of subunit B, the exact combination of which is needed for proper functioning. The B subunit in particular seems to play an especially important role in that a side arm of the protein (a single amino acid) protrudes from the rest of the protein, like a barrier across a gateway, narrowing the passageway to prevent ions from passing through the channel. This finding is novel and additional to narrow areas in the A subunit, which had been previously thought to be the only ones. The authors hope that study of the structure of cyclic nucleotide-gated ion channels will guide the search for molecules that could influence the channel to close completely, thereby preventing photoreceptor degeneration in diseases such as retinitis pigmentosa.

Merged particles after 2D classification (N = 165062)

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Barret DCA, Schertler GFX, Kaupp UB, et al. "The structure of the native CNGA1/CNGB1 CNG channel from bovine retinal rods." Nature Structural & Molecular Biology.  30 December 2021. https://doi.org/10.1038/s41594-021-00700-8