Rhodopsinlike

Rhodopsin-like, sometimes written rhodopsinlike or rhodopsin-like GPCRs, refers to a large superfamily of G protein-coupled receptors (GPCRs) known as class A or rhodopsin-like receptors. The prototypical member is rhodopsin, the visual pigment in vertebrate retina, but the family includes receptors for a wide range of ligands, including neurotransmitters, hormones, chemokines, and odorants.

Structure and motifs: Each receptor typically consists of seven transmembrane α-helices connected by extracellular and intracellular loops, with an extracellular N-terminus and an intracellular C-terminus. Conserved motifs common to class A GPCRs include the CWxP motif in transmembrane helix 6, the DRY motif at the cytoplasmic end of helix 3, and the NPxxY motif near the end of helix 7. A lysine residue in transmembrane helix 7 forms a Schiff base with retinal in visual opsins; in non-visual rhodopsin-like receptors there is no covalent chromophore, and ligands bind non-covalently.

Function and signaling: Activation begins when a ligand binds within the extracellular pocket, inducing conformational changes that enable coupling to heterotrimeric G proteins (Gs, Gi/o, Gq/11, or G12/13). This triggers downstream signaling cascades through second messengers such as cyclic AMP, IP3, calcium, or Rho-mediated pathways, varying with the G protein subtype and effector enzymes involved. Ligands range from small molecules to peptides and large odorants.

Evolution and distribution: Rhodopsin-like GPCRs are the largest gene family in many animals, with extensive diversification of sensory and regulatory receptors, notably including olfactory receptors. While they share a seven-transmembrane topology with microbial rhodopsins, they are evolutionarily distinct and function as signal receptors rather than photochemical ion pumps or channels.

Clinical relevance: Because of their central role in physiology, rhodopsin-like GPCRs are major drug targets, with therapies addressing cardiovascular, neurological, endocrine, and sensory systems. Advances in structural biology have illuminated ligand binding and activation mechanisms, aiding drug design.