“A Novel Photoactive Anion Channel: How Evolution is Able to Devise New Ways to Use Rhodopsin”

Rhodopsins are light-regulated membrane proteins found across all domains of life, including bacteria, eukarya, and archaea. Typically, rhodopsins consist of seven transmembrane helices (7TMs) with a covalently bound retinal chromophore. Microbial rhodopsins (type 1) serve a diverse range of biological functions, including acting as light-driven proton or ion pumps, light-gated ion channels, and light sensors. In contrast, animal rhodopsins (type 2) primarily function as G-protein-coupled receptors (GPCRs) that initiate G-protein signaling cascades. Animals utilize these rhodopsins for various physiological processes, such as vision and the regulation of biological rhythms. Upon capturing light, retinal isomerizes differently in the two families: from all-trans to 13-cis in type 1 rhodopsins, and from 11-cis to all-trans in type 2 rhodopsins.

This talk will focus on a recently discovered subfamily of rhodopsins with a unique structure from unicellular algae. This new family was identified using a metagenomics approach. Rozenberg et al. [1] revealed the distinct domain composition of these rhodopsins, which was determined by cryogenic electron microscopy (cryo-EM). The discovered complex is composed of two different rhodopsins linked in tandem and then fused to another protein, bestrophin. Bestrophins are anion or cation channels found in animals, bacteria, fungi, and green plants. The rhodopsin-rhodopsin-bestrophin (RRB or bestrhodopsin for short) fusion forms a pentameric mega-complex, with a bestrophin channel surrounded by five rhodopsin dimers, each binding a retinal chromophore. The retinal photoisomerization cycle in this complex is distinct from that of other known rhodopsins, featuring a unique chromophore-binding pocket. The bestrhodopsins were found to be photoactive and function as anion channels.

This talk will delve into the structural, biophysical and ion-conduction of the newly reported family of bestrhodopsins.

 

[1]      A. Rozenberg et al., “Rhodopsin-bestrophin fusion proteins from unicellular algae form gigantic pentameric ion channels,” Nat. Struct. Mol. Biol., vol. 29, no. 6, pp. 592–603, Jun. 2022, doi: 10.1038/s41594-022-00783-x.