Opioid receptors (OpR) are a Subfamily A4 G protein-coupled receptors with opioids as ligands[1]. OpR types are classified according to the ligands which bind to them.
You can check out the in the window on the right. It shows the mu opioid receptor bound to a peptide ligand and a G protein . The G protein ("G" because it binds to GTP) consists of three parts A , B , and C ).
- The μ-opioid receptor binds morphine. For more details on μ-opioid receptor see
The binding of an opioid induces a 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. .
The κ-opioid receptor is a . The extracellular side is home to the proteins primary . These 2 units will span the length for the cell membrane to form the basis of the receptor molecule. , 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, , 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 to ). 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 formed by Cys131 and Cys210 which is conserved across all opioid receptors. 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.
Opioid receptors typically have 2 big portions: the upper portion, zoomed in here with shown in indigo, that is ligand specific and recognizes a particular ligand, and the lower portion which is highly conserved amongst all receptors. When approaches δ-opioid receptor, it is distinguished by the high hydrophobic interaction between the indole group on the ligand and leucine 300 on the receptor. As it glides deeper into the binding site facilitated by the hydrophobic interaction, the hydroxyl group of the tyrosine-like phenol group hydrogen bonds with water molecules which are hydrogen bound to a critical histidine 248. This holds the ligand by having both the phenol group and histidine anchored by a water molecule. The water molecules within the binding pocket flank both the ligand and receptor, serving almost as a scaffolding on which for both components to act. Adjacent to the phenol group, the oxygen of an ether is hydrogen bound to tyrosine 129 of the receptor. On the opposite side of the binding site, Asp128 forms a salt bridge with the charged amino group on the ligand. The rest of the ligand maintains hydrophobic contact with non-polar residues of the binding site. The phenol to water interaction is a conserved interaction between many opioid receptors and their respective ligands as evidenced by many natural antagonists having a tyrosine that interacts with a water molecule in a similar fashion.
- The Nociceptin/orphanin FQ opioid receptor binds the heptadecapeptide orphanin[2].
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