Shining light on rhodopsin selectivity: How do proteins decide whether to transport H+ or Cl-?

Abstract

The versatile microbial rhodopsin family performs a variety of biological tasks using a highly conserved architecture, making it difficult to understand the mechanistic basis for different functions. Besaw et al. now report structures of a recently discovered cyanobacterial Cl^--pumping rhodopsin and its functionally divergent mutant that reveal how these transmembrane proteins create a gradient of activity with subtle changes. These insights are paralleled by a second recent report, which in combination answers long-standing questions about rhodopsin selectivity and will facilitate future engineering efforts.

Figure 1.

The structures of MastR and its H⁺-pumping mutant (MastR T74D) compared with the outward H⁺ pump, BR. Shown are the X-ray crystallographic structures of MastR (PDB code 6XL3), the H⁺-pumping MastR T74D mutant (PDB code 6WP8) (6), and BR (PDB code 1IW6) (8) (top) with an enlarged view of the region around the retinal Schiff base and the first two motif residues (bottom). The motif residues are indicated by letters circled in red. Cl⁻ and water molecules are shown as green and cyan spheres, respectively. The dashed lines indicate hydrogen bonds connecting the retinal Schiff base and amino acids of each motif. CP, cytoplasmic side; EC, extracellular side. The structures of proteins were illustrated by CueMol software (RRID:SCR_019052).