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Fig. 1 | Biology Direct

Fig. 1

From: Eukaryotic G protein-coupled receptors as descendants of prokaryotic sodium-translocating rhodopsins

Fig. 1

Structure-guided alignment of GPCRs and MRs. a, b, structural superposition of the entire structures of the sodium-translocating microbial rhodopsin KR2 (PDB: 4XTL, green) and the Na+-bound δ-opioid receptor δ-OR (PDB: 4N6H, blue), constructed using the PDBeFold tool [53]; the RMSD is 3.8 Å over 189 aligned residues with 14 % identity. The Na+ ion in the δ-OR structure is shown as a pink sphere. The retinal molecule bound to KR2 lysine residue is shown in grey. a, side view; b, top view from the extracellular side, the structures were cut along the dashed line. c-e, Na+-binding sites of the Na+-bound δ-opioid receptor δ-OR (panel c, PDB: 4N6H, cyan) [26], the sodium-translocating microbial rhodopsin KR2 (panel E, PDB 4XTL, green, the helices of KR2, as in other MRs, are denoted by letters from A to G) [40], and their superposition (panel d). Residue numbers are according to the Ballesteros–Weinstein nomenclature [56, 57]. Residues involved in coordination of Na+ ions in 4N6H (panel c) and 4XTL (panel e) are shown as sticks; the Na+ ion (panels c, d) and the imino group of the Schiff base (panels d, e) are shown as pink and blue spheres, respectively; water molecules are shown as small red spheres. The retinal molecule in panels d and e is shown in grey. For the visualization purposes only, we used the PDBeFold algorithm [53] to construct a superposition of KR2 and δ-OR with helices 4 and 5 removed. The resulting superposition provided a better overlap in the Na+-binding area with a local RMSD of 2.97 Å over 135 residues. F, structure-guided multiple sequence alignment of helices 3/C, 6/F, and 7/G of MRs and GPCRs. PDB: 3QAP, sensory rhodopsin II [93]; PDB: 3UG9, channelrhodopsin [94]; PDB: 2JAF, halorhodopsin [95]; PDB: 4HYJ, proton-pumping bacteriorhodopsin, [96]; PDB: 3DDL, xanthorhodopsin [30]; PDB: 4XTL, sodium pumping rhodopsin (KR2) [40]; PDB: 4N6H, δ-opioid receptor (δ-OR) [26]; PDB: 4DKL, μ-opioid receptor [97]; PDB: 4BVN, β1-adrenoceptor [28]; PDB: 2RH1, β2-adrenoreceptor [98]; PDB 4EIY, A(2A) adenosine receptor [42]; PDB: 3VW7, protease-activated receptor 1 [25]; PDB: 4BUO, neurotensin receptor 1 [99]; PDB: 1U19, visual pigment rhodopsin [100]. The boxes indicate positions corresponding to the known Na+-binding residues in GPCRs (see also Additional file 1: Figure S1, S4 for a complete structure-based sequence alignment and Additional file 1: Figure S5 for a multiple structural superposition). The residues that are involved in Na+ binding, as inferred from structural or mutation data [16, 2528, 38, 40, 41, 51] are colored red. The retinal binding Lys residues of bovine eye rhodopsin and MRs are indicated by blue arrows. Aromatic amino acids are shaded violet, proline is shaded gray, tyrosine is shaded green, other residues capable of forming hydrogen bonds are shaded by different colors depending on their electric charge

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