Ligand channel in pharmacologically stabilized rhodopsin

A look at how we see

20 August 2018

Research into molecules able to rescue degenerating vision is yielding insights into the protein structures that enable us to see.

Retinitis pigmentosa is a degenerative eye disease arising from the incorrect maturation of the retinal rod cell protein opsin and its resulting instability. Now, a Swiss team led by Roche scientists has used computational modeling and in vitro screening techniques to discover molecules, such as S-RS1, capable of ‘rescuing’ opsin; stabilizing and moving it to its correct location within rod cells. In doing so, the team identified a previously-unknown physical conformation of the protein which may facilitate its binding to the light-sensing molecule retinal. Retinal bound to opsin forms rhodopsin, a crucial component of human sight.

In elucidating opsin’s structure, and how S-RS1 binds and modifies the protein, this research helps to deepen our understanding of the molecular biology underpinning degenerative eye conditions and helps to shed light on potential treatments.

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References

1. Proceedings of the National Academy of Sciences of the USA 115, 3640–3645 (2018). doi: 10.1073/pnas.1718084115