Receptor

spinqualitylabelsall models Nicotinic Acetylcholine Receptor, PDB code 2bg9 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Under development!!! Transmembrane (cell surface) receptors See also Membrane proteins. Ion channel-linked (ionotropic) receptors These receptors are typically the targets of fast neurotransmitters such as acetylcholine (nicotinic) and GABA; activation of these receptors results in changes in ion movement across a membrane. Ionotropic receptors 5-hydroxytryptamine receptor#Structural highlights/Specific Function of 5-HT3 The extracellular subunit interface of the 5-HT3 receptors: a computational alanine scanning mutagenesis study 5-hydroxytryptamine receptor#5-HT3 receptor antagonists 5-HT3 receptor The 5-HT3 receptor is bullet-shaped and consists of five subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the five subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of three regions; the extracellular region, the transmembrane region, and the intracellular region. The extracellular region is relatively large compared to the other two regions, and contains a short C-terminus and a larger N-terminus. The N-terminus of the extracellular region is where the ligand binding occurs, and therefore deals with the agonists and antagonists. These binding sites are located between two bordering subunits, assembled from three alpha-helices of one subunit and three beta-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing away from the binding pocket. This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them. The transmembrane region is within the C-terminus region, and contains four alpha-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These four alpha-helical domains conduct the channel openings via ion selectivity, depending on both charge and size. M2, the porous domain, contains rings of charged amino acids at both its start and its end, accounting for M2’s main contribution to ion selectivity. The M3 and M4 alpha-helices create a large loop with one another, thus assembling the intracellular region. The extracellular subunit interface of the 5-HT3 receptors: a computational alanine scanning mutagenesis study The serotonin type-3 receptor (5-HT3-R) is a cation selective transmembrane protein channel that belongs to the Cys–loop Ligand-Gated Ion Channel (LGIC) superfamily (https://www.ebi.ac.uk/compneur-srv/LGICdb/LGICdb.php), which also includes receptors for nicotinic acetylcholine (nAChR, PDB code 2bg9), γ-aminobutyric acid and glycine. 5-HT3-R is involved in signal transmission in the central and peripheral nervous system and its malfunctioning leads to neurodegenerative and psychiatric diseases, therefore it is an important target for drug design research. A few drugs active against 5-HT3-R are already on the market, such as, for example, palonosetron (https://en.wikipedia.org/wiki/Palonosetron) and granisetron (https://en.wikipedia.org/wiki/Granisetron). The 5-HT3R is made of five monomers assembled in a pseudo-symmetric pentameric shape to form an ion channel permeable to small ions (Na+, K+); each subunit contains three domains: an intracellular portion, a transmembrane domain and an extracellular region (shown on the example of nAChR, 2bg9). To date, five different 5-HT3-R subunits have been identified, the 5-HT3 A, B, C, D and E; however, only subunits A and B have been extensively characterised experimentally. The ligand binding site of nAChR is located at the extracellular region, at the interface between two monomers (α-γ and α-δ; 2 identical α monomers, chains A and D, are colored in same color - lavender), called the principal and the complementary subunits. The 3D structure of 5-HT3-R has not been experimentally solved yet; however, it has been obtained computationally by means of homology modelling techniques. (https://salilab.org/modeller/) Thus, the extracellular region of the 5HT3 subunits A and B are modelled by homology with the 3D structure of the nAChR subunit A (2bg9-A) and are used to assemble receptor structures as pseudo-symmetric pentamers made either of five identical subunits A (homomeric 5-HT3A-R) or of both subunits A and B (heteromeric 5-HT3A/B-R in the BBABA arrangement) in a still debated arrangement. Subunits A and B are colored in magenta and red, respectively. A complete characterization of the extracellular moiety of the dimer interface of the 5-HT3-R (AA dimer is shown, principal subunit is colored in cyan and complementary is in blue, is obtained by the Computational Alanine Scanning Mutagenesis (CASM) approach , which simulates the substitution, one by one, of all the amino acid residues at the subunit-subunit interfaces with an Ala, thus to assess the interface binding contribution of single residue side-chains. The most relevant residues for interface stabilization are classified as “hot spots” that stabilize the interface by more than 4 kcal/mol and “warm spots” that contribute to interface stabilization by more than 2 kcal/mol. Click here to see also the interface of complementary subunit. Interface residues are shown in spacefill representation, hot spot residues are colored in red and warm spots residues are are in orange. From this analysis the important aromatic cluster located at the interface core and formed by residues W178 (principal subunit), Y68, Y83, W85 and Y148 (complementary subunit) is highlighted. In addition, two important groups of interface residues are probably involved in the coupling of agonist and antagonist binding to channel activation/inactivation: W116-H180-L179-W178-E124-F125 (principal subunit) and Y136-Y138-Y148-W85-(P150) (complementary subunit), where W178 and Y148 appear to be critical residues for the binding/activation mechanism. Finally, the comparison of the AA interface with the BB interface (principal subunit of AA is colored in cyan, principal subunit BB is colored in darkmagenta, complementary subunit AA is in blue and complementary subunit BB is in magenta) shows differences which could explain the reasons why the homopentamer 5-HT3B-R, if expressed, is not functional. Nicotinic Acetylcholine Receptors in general Alpha-bungarotoxin is a nicotinic cholinergic antagonist that is found within the venom of Bungarus multicinctus, a South-asian snake belonging to a group commonly known as kraits. Binding site of AChR Acetylcholine Receptor and its Reaction to Cobra Venom AMPA glutamate receptor by University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground. Glutamate receptor (GluA2) G protein-linked (metabotropic) receptors This is the largest family of receptors and includes the receptors for several hormones and slow transmitters(dopamine, metabotropic glutamate). They are composed of seven transmembrane alpha helices. The loops connecting the alpha 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 G protein-coupled receptors Neurotensin receptor CXC chemokine receptor type 4 Mu Opioid Receptor Bound to a Morphinan Antagonist μ Opioid Receptors Mu Opioid Receptor The κ-opioid receptor binds opium-type ligands. For details see Student Project 3 for UMass Chemistry 423 Spring 2015. T The δ-opioid receptor binds enkephalins. For details see Delta opioid receptor Tutorial: The opioid receptor, a molecular switch Orexin and Orexin receptor Belsomra and Orexin receptors Hypocretin and receptors Human Follicle-Stimulating Hormone Complexed with its Receptor GPR40 Lysophosphatidic acid receptor Sphingosine 1-phosphate Receptor Rhodopsin Rhodopsin Structure and Function Serotonin receptors, main page 3D structures of Serotonin receptors Adrenergic receptors in general Beta-1 Adrenergic receptor Dobutamine, see Beta-1 Adrenergic receptor, 2y00, 2y01, 6h7l Isoprenaline, see Beta-1 Adrenergic receptor, 2y03 Carmoterol, see 2y02 Salbutamol (Albuterol in USA), 2y04 The human β2 adrenergic receptor bound to a G-protein (3sn6) is featured in a scene above, and additional structures are on the Adrenergic receptor page. Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky Group:SMART:A Physical Model of the beta-Adrenergic Receptor Gs: adenylate cyclase activated, cAMP up. For Gs see Beta2 adrenergic receptor-Gs protein complex updated Dopamine receptors 1 page Dopamine receptors 2 page Histamine H1 receptor 3rze - human histamine H1 receptor with an antagonist doxepin Adenosine A2A receptor Effect of Caffeine (Trimethylxanthine) on Human A2A Receptor Adenosine A2A receptor 3D structures Muscarinic acetylcholine receptor Glucose-dependent Insulinotropic Polypeptide Receptor Glucagon receptor Glucagon-like peptide 1 receptor Metabotropic Glutamate Receptors Ligand Binding N-Terminal of Metabotropic Glutamate Receptors Metabotropic glutamate receptor 5 Kinase-linked, enzyme-linked and related receptors Receptor tyrosine kinases Receptor tyrosine kinases (RTKs) are part of the larger family of protein tyrosine kinases. They are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Approximately 20 different RTK classes have been identified. RTK class I Epidermal Growth Factor Receptor family RTK class II Insulin receptor family RTK class III Platelet-derived growth factor receptor family RTK class IV Vascular Endothelial Growth Factor Receptor family RTK class V Fibroblast growth factor receptor family RTK class VIII Hepatocyte growth factor receptor family RTK class IX Ephrin receptor family RTK class XIII Epithelial discoidin domain-containing receptor (DDR receptor) family Neurotrophin: High affinity nerve growth factor receptor (or Tyrosine kinase receptor) and TrkB tyrosine kinase receptor Insulin-like growth factor receptor Enzyme-linked receptor TGF-beta receptor Activin receptor Crystal structure of the extracellular domain of the receptor-like kinase TMK3 from Arabidopsis thaliana Bone Morphogenetic Protein 7 and receptor Neurotrophin High affinity nerve growth factor receptor TrkA TrkB tyrosine kinase receptor Toll-like Receptors Immune receptors Leukocyte immunoglobulin-like receptors Leukocyte immunoglobulin-like receptor Cytokine receptors TNF receptor superfamily Tumor necrosis factor receptor TRAIL (TNF-related apoptosis-inducing ligand) or TNF ligand superfamily 10 Type I cytokine receptors Erythropoietin receptor Prolactin receptor Type II cytokine receptors Interferon receptors Interferon receptor Structural linkage between ligand discrimination and receptor activation by type I interferons Multiple sclerosis and Interferon Receptors Interleukin receptors Interleukin receptor Interleukin-20 receptor: Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1 T-cell receptors T-cell receptor SP3.4-TCR-HLA-DQ8-α-1-gliadin complex TGF-beta receptor TGF-beta receptor LDL receptor LDL receptor Transferrin receptor Transferrin receptor Intracellular receptors Signal recognition particle receptor Signal recognition particle receptor Receptor for activated C kinase 1 Receptor for activated protein kinase C 1 Nuclear receptors Nuclear receptors Thyroid hormone receptor Retinoic acid receptor RA Mediated T-reg Differentiation; Retinoic acid acts as the ligand for the Retinoic Acid Receptor-α (RARα) / Retinoid X Receptor-α (RXRα) heterodimer PPAR-gamma Pioglitazone is a selective agonist for Peroxisome Proliferator-Activated Receptor Gamma Liver X receptor Bile acid receptor Vitamin D receptor Pregnane X receptor Retinoid X receptor Estrogen receptor Ivan Koutsopatriy estrogen receptor Estrogen receptor#Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs Estrogen receptor#Estrogen receptor α complexed with raloxifene and a corepressor peptide Tamoxifen and the Estrogen receptor Student Project 10 for UMass Chemistry 423 Spring 2015 Estrogen-related receptor Glucocorticoid receptor Mineralocorticoid receptor Progesterone receptor Androgen receptor Liver receptor homolog-1? Endoplasmic reticulum/Sarcoplasmic reticulum receptors Ligand-gated Calcium channels Ryanodine receptor SEE ALSO: Hormones and their receptors Hormone Growth factors Neurotransmitters

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