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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University.

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Presentation on theme: "Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University."— Presentation transcript:

1 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2 G-PROTEIN-LINKED RECEPTORS Tímea Berki and Ferenc Boldizsár Signal transduction Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

3 TÁMOP-4.1.2-08/1/A-2009-0011 Nomenclature G-protein-coupled receptors (GPCRs) Seven-transmembrane domain receptors 7-TM receptors Heptahelical receptors Serpentine receptor G protein-linked receptors (GPLR)

4 TÁMOP-4.1.2-08/1/A-2009-0011 Ligand-binding Gα C-terminal tail Other Gα surfaces Helix 8 (G β  -binding) Gα -binding Interaction surface IL1IL2IL3 EL1EL3EL2 Extracellular loops (EL1-3) Intracellular loops (IL1-3) N C GRK phosphorylation (Desensitization) PKC phosphorylation (Desensitization) PKC phosphorylation (Desensitization) Palmitoylation (Lipid raft localization) N-Glycosylation (Receptor folding, trafficking) E/DRY Motif (Receptor activity and protein-protein interactions) Plasma membrane TM 1 TM 2 TM 3 TM 4 TM 5 TM 6 TM 7 Transmembrane helix (TM1-7) TM 4 7-transmembrane-spanning receptors (7-TM)

5 TÁMOP-4.1.2-08/1/A-2009-0011 GPCR

6 TÁMOP-4.1.2-08/1/A-2009-0011 Structure of 7-TM receptors Side perspective Intracellular persective TM1 TM4 TM5 TM6 TM7 Helix 8 IL 1 IL2 IL3 EL1 EL2 EL 3 N C TM2 TM3 Intracellular loops Extracellular loops TM1 TM2 TM3 TM4 TM5 TM6 TM7 Helix 8 IL1 IL3 EL1 EL2 EL3 N C G  -binding surface Non-covalent bond IL2 TM1 TM2 TM4 Helix 8 IL1 IL2 IL3 EL1 EL2 EL3 N C TM7 TM6 TM3 TM5 GG GG TM1 TM5 TM6 TM7 Helix 8 N C TM4 TM2 GαGα GαGα TM3 GG GG C-terminal tail of G  Agonist Active GPCR Inactive GPCR

7 TÁMOP-4.1.2-08/1/A-2009-0011 GPCR subtypes Class A (or 1) – Rhodopsin-like Class B (or 2) – Secretin receptor family Class C (or 3) – Metabotropic glutamate/pheromone Class D (or 4) – Fungal mating pheromone receptors Class E (or 5) – Cyclic AMP receptors Class F (or 6) – Frizzeled/Smoothened

8 TÁMOP-4.1.2-08/1/A-2009-0011GDP      GTP  GTP    GDP    Plasma membrane Cytoplasm GDPGTP G-protein coupled receptor (GPCR) Signal molecule Inactive G-protein Activated G-protein subunits GTP    Activation of G-protein- coupled receptors (GPCR)

9 TÁMOP-4.1.2-08/1/A-2009-0011GDP      GTP Gi  G-protein coupled receptor (GPCR) Phospholipases Ion channels Activates Rho Ion channels PI3K Phospholipases Adenylyl cyclases Receptor kinases GTP Gs  GTP Gq  GTP G 12/13  GTP  Ca 2+ PLC PIP 2 DAG IP 3 cAMP Adenylyl cyclase Adenylyl cyclase ATPcAMP Adenylyl cyclase Adenylyl cyclase ATP Plasma membrane Cytoplasm G-proteins

10 TÁMOP-4.1.2-08/1/A-2009-0011 G-protein heterotrimer

11 TÁMOP-4.1.2-08/1/A-2009-0011 Catecholamine hormon synthesis CO 2 – +H3N+H3N OH Tyrosine Tyrosine hydroxylase CO 2 – +H3N+H3N OH Dihydroxy phenilalanine (L-DOPA) OH DOPA decarboxylase Dopamine +H3N+H3N OH Dopamine β -hydroxylase Dopamine +H3N+H3N OH HO Phenethanolamine N-methyltransferase Epinephrine N OH HO H2+H2+ H3CH3C

12 TÁMOP-4.1.2-08/1/A-2009-0011 Epinephrine and analogues HO OH CH 3 H N Epinephrine (adrenaline) Tyramine HCL HO NH 2.HCL OH CH 3 H N Ephedrine sulphate CH 3 2.H 2 SO 4 Pseudoephedrine HCL OH CH 3 H N.HCL Dexamfetamine sulfate NH 2 CH 3 2.H 2 SO 4 Amfetamine sulfate NH 2 CH 3 2.H 2 SO 4 Phenylethanolamine sulfate NH 2 OH 2.H 2 SO 4 Isoprenaline HCL N OH.HCL H HO CH 3 Orciprenaline sulfate N OH H HO OH CH 3.H 2 SO 4 2 2 Salbutamol sulfate N OH H HO CH 3 HO CH 3.H 2 SO 4 2 Terbutaline sulfate N OH H CH 3 HO OH

13 TÁMOP-4.1.2-08/1/A-2009-0011 cAMP-PKA pathway PO 4 gated channel Gα gated channel cAMP gated channelReceptor Inactive PKA ActivatedPKA GTP    Adenylyl cyclase Adenylyl cyclase R R C C C C cAMPcAMP cAMPcAMP R R C C C C RcAMPcAMP RcAMP cAMP CRE CREB cAMP Response Element Gene expression P CREB P ATP cAMP GTP  Nucleus P cAMP GTP  P ADP ATP

14 TÁMOP-4.1.2-08/1/A-2009-0011 Primary Action of Epinephrine in a Liver CellAcetylcholine Stress signal Fuel for „fight or flight” Protein Kinase A Glucose-6- Phosphatas e Pyr Kinase Fructose-2,6- bisphosphatase Fructose-2,6- bisphosphatase Pyruvate PEP Fructose- 1,6-bisP Fructose- 6-P Fructose-2,6-bisP Glucose-6- P Glucose Glucose-1- P Glycogen Glucogen Phosphoryl ase Glucogen Phosphoryl ase Glucogen Synthase P P P Phosphoryl ase Kinase A Phosphoryl ase Kinase A P P cAMPATP Adenylate Cyclase GDP   ss Epinephri ne Receptor

15 TÁMOP-4.1.2-08/1/A-2009-0011 Glucagon signalingPANCREAS Glucose low in blood Protein Kinase A Glucose-6- Phosphatas e Pyr Kinase Fructose-2,6- bisphosphatase Fructose-2,6- bisphosphatase Pyruvate PEP Fructose- 1,6-bisP Fructose- 6-P Fructose- 2,6-bisP Glucose-6- P Glucose Glucose-1- P Glycogen Phosphoryl ase Glycogen Phosphoryl ase Glycogen Synthase P P P P cAMPATP Adenylate Cyclase GDP   ss Glucagon (Epinephri ne) Receptor

16 TÁMOP-4.1.2-08/1/A-2009-0011 Serotonin receptor Serotonin receptor Serotonin receptor → G-protein → adenylyl cyclase → ATP → cAMP → PKA → cAMP Response Element (CRE) → Gene expression

17 TÁMOP-4.1.2-08/1/A-2009-0011 Types of serotonin receptor FamilyMechanismPotential 5-HT1Decreasing cellular levels of cAMPInhibitory 5-HT2Increasing cellular levels of IP3 and DAGExcitatory 5-HT3Depolarizing plasma membraneExcitatory 5-HT4Increasing cellular levels of cAMPExcitatory 5-HT5Decreasing cellular levels of cAMPInhibitory 5-HT6Increasing cellular levels of cAMPExcitatory 5-HT7Increasing cellular levels of cAMPExcitatory

18 TÁMOP-4.1.2-08/1/A-2009-0011 Receptor desensitization GRK ATPADP Arrestin P PP P PP G-protein linked receptor kinase Activated receptor Desensitized receptor


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