Signal transduction

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! Ligand Types of ligands Hormones and their receptors Hormone Growth factors Neurotransmitters Receptor Ion channels Chemical communication in arthropods Proton Channels Neuronal Nitric Oxide Synthase (Nos1) is functioning in cell signaling and communication - a vital part of the nervous tissue. Chloride Ion Channel Chloride Intracellular Channel Protein 2 Ivermectin bound to Glu gated chloride channel Membrane Channels & Pumps Ryanodine receptor Lipid signaling: Ceramide Sphingomyelinase (SMase) or sphingomyelin phosphodiesterase is a hydrolase involved in sphingolipid metabolism. It catalyzes the breakdown of sphingomyelin (SM) to phosphocholine and ceramide. Acid-beta-glucosidase or glucosylceramidase is a lysozomal enzyme (EC number 3.2.1.45), which cleaves glucosylceramide to glucose and ceramide. It catalyzes hydrolysis of the sphingolipid, glucosylceramide (GlcCer), to glucose and ceramide at the acidic pH prevailing within the lysosome. Click here to see animation of this reaction. The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. Sphingosine-1-Phosphate Lysophosphatidic acid receptor#Sphingosine 1-Phosphate Receptor Glucosylceramide Acid-beta-glucosidase Phosphatidylinositol bisphosphate (PIP2) Phosphatidylinositol 4,5-bisphosphate (PIP2) binds to and directly activates inwardly rectifying potassium channels. Inward rectifier KCh. Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Phospholipase C beta 3 The Structure of PI3K Epsin Phosphoinositide 3-Kinases PI3K Activation, Inhibition, & Medical Implications Prostaglandins Prostaglandin D synthase Prostaglandin E synthase Cyclooxygenase Prostaglandin-E2 9-reductase Prostaglandin F synthase Leukotriene B4 hydroxydehydrogenase Aldo-keto reductase Endocannabinoids Beta-2 adrenergic receptor Monoglyceride lipase GPR40 Lysophosphatidic acid receptor#Endocannabinoid Receptor 1 Fatty acid amide hydrolase Retinol derivatives Retinal Rhodopsin Rhodopsin Structure and Function The BioMolViz Project Bacteriorhodopsin CRABP I ( Cellular Retinoic Acid Binding Protein ) Retinal dehydrogenase User:Rick H. Cote/PDE6#PDE6: central effector of visual excitation in retinal rod and cone photoreceptors Transducin Pikachurin Retinoid isomerohydrolase Retinoic acid Retinoic acid receptor Cellular retinoic acid-binding protein CRABP I ( Cellular Retinoic Acid Binding Protein ) NK cell receptor Retinoid X receptor RA Mediated T-reg Differentiation PPAR-gamma Student Project 2 for UMass Chemistry 423 Spring 2015 Aldehyde dehydrogenase Steroid Hormones and their receptors This large and diverse class of steroids are biosynthesized from isoprenoids and structurally resemble cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands. For example, estradiol is an important estrogen steroid hormone in both women and men. It is a typical steroid with core four-ring system (ABCD), composed of 17 carbon atoms. Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes. Prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Glucocorticoids Mineralocorticoids Pentaerythritol tetranitrate reductase active site contains the cofactor FMN and the substrate steroid prednisone. Water molecules are shown as red spheres. Whole active site. Corticosteroid-binding globulin Cortisol (hydrocortisone) is a corticosteroid with both glucocorticoid and mineralocorticoid activity and effects. Glucocorticoids Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor. Dexamethasone is a glucocorticoid medication. It is the most potent glucocorticoid and it has not mineralocorticoid potency. Glucocorticoid receptor. Human glucocorticoid receptor ligand-binding domain bound to dexamethasone (1m2z). Forkhead box proteins (FOX) are transcription factors involved in regulation of gene expression.. FOXO1 activation contributes to glucocorticoid-induced beta cell death. FOX contain a DNA-binding motif (DBD) of 80-100 amino acids having a winged-helix shape. Human FoxO1 DNA-binding domain with DNA, Ca+2 and Cl- ions. Ca coordination site. Water molecules shown as red spheres. Cl coordination site. Nuclear receptor coactivator (NCOA) is a protein recruited by nuclear receptors in order to enhance or repress DNA transcription. NCOA is involved in coactivation with transcription factors. NCOA1 shows histone acetyltransferase activity and is required for steroid hormone response. NCOA2 is a DNA transcription coactivator with glucocorticoid receptor. NCOA/STAT6 transactivator domain LXXLL peptide interactions. 1st Iod coordination site. 2nd Iod coordination site. Water molecules are shown as red spheres. 3th and 4th Iod coordination sites. 5th Iod coordination site. Thioredoxin Reductase (TrxR) is an enzyme which reduces thioredoxin using NADPH. Mutations in TrxR-2 are associated with familial glucocorticoid deficiency. Thioredoxin Reductase (TrxR) is an enzyme which reduces thioredoxin using NADPH. TrxR-2 is mitochondrial. For more details see User:Sarah Abdalla/Thioredoxin Reductase. TrxR and Trx form an intramolecular Cys-Cys bond. FAD binding site. Water molecules are shown as red spheres. Microsomal Prostaglandin E synthase (PGES) converts cyclooxygenase (COX)-derived prostaglandin to PGE2. It is membrane-associated and belongs to the microsomal glutathione S-transferase family. PGES is preferentially linked with the inducible COX-2 . PGES is induced by proinflammatory stimuli and down-regulated by anti-inflammatory glucocorticoids. Microsomal Prostaglandin E synthase is membrane-associated (coordinates are from OPM database. The anti-inflammatory inhibitor binds to PGES in a pocket above the glutathione and interacts with various side-chains of a helix. Water molecules are shown as red spheres. Mineralocorticoids Mineralocorticoids are a class of corticosteroids. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mineralocorticoid is aldosterone. Mineralocorticoid receptor (MR) in epithelial cells is activated by the mineralocorticoid hormone aldosterone promoting renal sodium retention and potassium excretion. It is nuclear receptor. In non epithelial cells MR is activated by cortisol. MR is exposed to many steroids including cortisol, cortisone and progesterone, however, aldosterone and deoxycorticosterone are its physiological ligands. MR mutations are the principal cause of renal pseudohypoaldosteronism. MR mutation S810L causes early-onset hypertension. Inhibition of cardia MR prevents doxorubicin-induced cardiotoxicity. MR is an important proadipogenic transcription factor that may mediate aldosterone and glucocorticoid effects on adipose tissue development and hence on obesity and development of metabolic syndrome. The MR ligand aldosterone binds in a fully enclosed pocket, contacting residues with six α-helices and a β-turn (Alpha Helices, Beta Strands , Loops ,Turns). It forms hydrogen bonds with 4 MR residues. Whole binding site. Water molecules are shown as red spheres. Angiotensin-Converting Enzyme, Renin-Angiotensin-Aldosterone System. Hydroxysteroid dehydrogenase Lysophosphatidic acid receptor GPR40 Signaling Pathways: ABA Signaling Pathway ABA Signaling Pathway PYR/PYL/RCAR family of ABA receptors Protein Phosphatase 2C ABA-regulated SNRK2 Protein Kinase Protein Kinases: Calcium-dependent protein kinase Calcium/Calmodulin-dependent protein kinase Eukaryotic Protein Kinase Catalytic Domain Interleukin-1 receptor-associated kinase Tyrosine kinase Receptor tyrosine kinases Tyrosine kinase Janus kinase or tyrosine-protein kinase JAK (JAK) are nonreceptor tyrosine kinases which transduces cytokine-mediated signals via the JAK-STAT pathway. The JAK-STAT pathway transmits signals through the cell membrane to DNA promoters thus causing transcription. Protein kinase C Protein kinase C The sensitization of TRPV1 is thought to be connected to phosphorylation by protein kinase C and the cleavage of PIP2. MAPK Mitogen-activated protein kinase Mitogen-activated protein kinase kinase Mitogen-activated protein kinase kinase kinase Michael Roberts/BIOL115/ERK2 p38 MAPK (UMass Chem 423 Student Projects 2011-2) CAMP-dependent protein kinase CAMP-dependent protein kinase CAMP Dependent Protein Kinase, Catalytic Subunit Protein Kinase A Chemotaxis: Chemotaxis protein, Histidine Kinase (HK) CheA relays signals from the transmembrane chemoreceptors (methyl-accepting chemotaxis proteins/MCPs) to regulate bacterial chemotaxis. Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima Molecular Playground/Bacterial Chemotaxis Receptors Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor Methyl-accepting chemotaxis protein Mechanotransduction: Fibronectin, Laminin, and Collagen can bind to receptors (integrins). CD44 is a glycoprotein involved in cell-cell interactions. CD44 is a receptor of hyaluronic acid (HA). Mechanosensitive channels are involved in touch, hearing, and in maintaining osmotic balance. Thermoception Heat Shock Proteins Transient receptor potential channels Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Voltage-gated channels Voltage-gated calcium channels Voltage-gated calcium channel Cav1.1 complex Potassium Channel Potassium channel toxin Visual phototransduction Light is detected by rhodopsin in rod and cone cells. Rhodopsin#Visual Signal Transduction Rhodopsin Structure and Function Photoreceptor pigments Retinal (in rhodopsin). Rhodopsin#Retinal Chromophore of Rhodopsin and Rhodopsin#Photoisomerization of 11-cis Retinal. Flavin (in cryptochrome). Cryptochrome 4 and JMS/cryptochrome. Circadian clock Circadian clock protein Circadian Clock Protein KaiC Period circadian protein Protein phosphatases: Protein Phosphatase 2C ABA-regulated Protein Phosphatase 2C Second messengers cAMP is second messenger Adenylyl cyclase (ADCY, EC number 4.6.1.1), also known as adenylate cyclase, is an enzyme which catalyzes the cyclization of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Catabolite gene activator protein CAMP-dependent protein kinase CAMP-dependent protein kinase CAMP Dependent Protein Kinase, Catalytic Subunit Protein Kinase A IP3 is second messenger Phospholipase C and PLC beta 3 Gq Receptors that activate this pathway (Phospholipase C) are mainly G protein-coupled receptors coupled to the Gαq subunit, including: 5-HT2 serotonergic receptors (5-hydroxytryptamine receptor#Structural highlights/Specific Function of 5-HT2B). α1 adrenergic receptors Calcitonin receptors Histamine H1 receptor. The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate signaling pathway. When a ligand binds to a G protein-coupled receptor that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG. Metabotropic glutamate receptor 1 and metabotropic glutamate receptor 5 belong to group I and activate phospholipase C. For details see Metabotropic glutamate receptor 5. M1, M3, and M5 muscarinic receptors. Muscarinic acetylcholine receptors (mAChR) contain 5 subtypes M1-M5. Subtypes M1, M3, M5 activate phospholipase C which leads to activation of protein kinase C. Inositol 1,4,5-Trisphosphate Receptor Paracrine signaling: fibroblast growth factor (FGF) family, Hedgehog family, Wnt family, and TGF-β superfamily Fibroblast growth factor and Fibroblast growth factor receptor (FGFR). FGFR belongs to Receptor tyrosine kinases, class V. Sonic Hedgehog Sonic Hedgehog Protein patched homolog 1 (Ptch1) acts as receptor of Sonic Hedgehog protein (Shh) which is involved in formation of embryonic structures. Ca2+ signalling processes Inositol 1,4,5-Trisphosphate Receptor Calcium-dependent protein kinase Calcium/Calmodulin-dependent protein kinase Protein kinase C H+/K+-ATPase signal pathway (acetylcholine, histamine, and gastrin) activates the pump in order to move the vesicles toward the lumen. Esomeprazole and H+/K+ - ATPase Interaction Proton pump Signal transducing adaptor proteins (STAPs) GRB, Growth factor receptor-bound protein and Grb10 SH2 Domain. MyD88, TIR domain-containing adapter protein. GTPase GTPase HRas. The Mitogen-activated protein kinase cascade MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. Mitogen-activated protein kinase Mitogen-activated protein kinase kinase Mitogen-activated protein kinase kinase kinase Michael Roberts/BIOL115/ERK2 p38 MAPK (UMass Chem 423 Student Projects 2011-2) Inflammatory response Aspirin Effects on Cyclooxygenase Cyclooxygenase Interleukin-10 YKL-40 Toll-like Receptors Phospholipase A2 C-X-C motif chemokine Cytokine receptors Allostery Hemoglobin Thrombin Molecular Playground/Caspase-7 Dynamics RNase A Oligomers ATPase ATPase

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