Receptor: Difference between revisions

This is the largest family of receptors and includes the receptors for several hormones and slow transmitters (dopamine, metabotropic glutamate). They are composed of 7 transmembrane α-helices. The loops connecting the α-helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop. These receptors are coupled to different intracellular effector systems via G proteins

The binding of an opioid induces a <scene name='78/786661/Mor_on_off/2'>conformational change</scene> in the μ-opioid receptor that activates an inhibitory G-protein (Gαi/o). This results in the dissociation of the G-protein complex. The Gα subunit then inhibits adenylyl cyclase. The Gβγ subunit acts to inhibit Ca2+ channels and activate K+ channels. <scene name='87/874998/Mor_on_off/1'>Activation mechanism</scene>.

The κ-opioid receptor is a <scene name='48/483884/K_or_general/1'>homodimer</scene>. The extracellular side is home to the proteins primary <scene name='48/483884/K_or_binding_general/2'>active site</scene>. These 2 units will span the length for the cell membrane to form the basis of the receptor molecule. <scene name='48/483884/K_or_dimmer_assembly/1'>The each subunit is attached to the other by the I, II and VIII α-helices</scene>, where helices I (in light blue) and helices VIII (in dark blue). This area will make up the basis for the intermembrane surface area. A distinguishing feature that separates the κ-opioid receptor from other receptors, is the large β-hairpin, <scene name='48/483884/K_or_beta_sheet/3'>ECL2</scene>, located near the main active site of the protein. It is believed that its function is to cap the active site of the receptor. Although in general, this protein is primarily composed of α-helices, not β-sheets (Compare <scene name='48/483884/K_or_beta_sheet/1'>β-sheet</scene> to <scene name='48/483884/K_or_alpha/1'>α-helices</scene>). This evidence reinforces the idea that this protein is a transmembrane protein rather than one found inside the cytosol. In general transmembrane protein are composed almost entirely of α-helices (or β-sheet arranged in special fashion called a β-barrel), in order to have maximum stability inside the membrane. Interesting feature of the κ-opioid receptor is the <scene name='48/483884/K_or_disulfide_bond/1'>disulfide bond </scene> formed by Cys131 and Cys210 which is conserved across all opioid receptors. <scene name='48/483884/K_or_ligand_biding_pocket_asp/1'>Active site</scene> of κ-opioid receptor. The human κ-opioid receptor ligand binding pocket displays a unique combination of key characteristics both shared with and distinct from those in the chemokine and aminergic receptor families.