Structural characterization of Bestrhodopsins – a novel family of gigantic light activated ion-channels

Rhodopsins are integral membrane proteins that bind retinal chromophores to form light-absorbing pigments. These proteins are ubiquitous in nature and play key roles in microbial physiology as well as animal visual perception. Here we report the discovery and characterization of a novel family of rhodopsins in alga - the bestrhodopsins, in which one- (or often two-) rhodopsin domain(s), are C-terminally fused to a bestrophin channel. Bestrophins are ion channels, best-known for their involvement in the development of the retinal pigment epithelium in humans and other animals. Cryo-EM analysis of bestrhodopsins revealed that it forms a pentameric megacomplex (~700 kDa) with ten rhodopsin units surrounding the channel in the center. We further demonstrate that the domain composition of bestrhodopsins accurately predicts their function as light regulated ion channels. The discovery of bestrhodopsins is thrilling, as such composition has never been found in nature, and apart from their yet to be discovered, physiological functions, these unique proteins pave the way for an entirely new strategy of designing optogenetic tools by which the light sensing and the ion-conducting modules are fused and can be modified independently to control a large array of brain functions. Here we will present the discovery, structure, biochemical and biophysical properties of this intriguing family of proteins.

Rozenberg, A., Kaczmarczyk, I., Matzov, D., Vierock, J., Nagata, T., Sugiura, M., ... & Shalev-Benami, M. (2022). Rhodopsin-bestrophin fusion proteins from unicellular algae form gigantic pentameric ion channels. Nature Structural & Molecular Biology, 29(6), 592-603.