Upload File

caffeine signaling via ligand-receptor binding agonist - ligand binding to a receptor and eliciting...

  • Home
  • Documents
  • Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor
23
N N N N CH 3 H 3 C O O CH 3 caffei ne Signaling via Ligand- Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor but not eliciting a response R + L ↔ R∙L K d = [R][L]/[R∙L]

Upload: lilian-walsh

Post on 21-Jan-2016

237 views

Category:

Documents


0 download

Report

Tags:

TRANSCRIPT

Page 1: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

N

N N

N

CH3H3C

O

O

CH3

caffeine

Signaling via Ligand-Receptor Binding

Agonist - ligand binding to a receptor and eliciting a response

Antagonist - ligand binding to a receptor but not eliciting a response

R + L ↔ R∙L

Kd = [R][L]/[R∙L]

Page 2: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Bacterial Quorum Sensing

Increased cell density dependant signaling

Activation of Bio-film formation which affects bacterial resistance

Page 3: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Extracellular Signals

Page 4: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

G Protein Coupled Receptors

Guanyl nucleotide binding protein:Minus ligand, α, β, and γ subunits associated with GDP (inactive bound form) and

Plus ligand, α subunit exchanges for GTP (active released form)

Signal propagation: Activate adenylate cyclase converts ATP to cyclic ATP

Signal resetting:GTP hydrolyzed to GDP and β, and γ subunits re-associate

Page 5: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

G-Protein Cycle and Generation of Cyclic AMP

How is adenylate cyclase activated?

Page 6: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

External Signal for G-Protein Activation

β2-adreneric receptor

Page 7: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Heterotrimeric G Protein

α, β, and γ subunits (blue, green, and yellow, respectively) associated with GDP (orange)

Page 8: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

G-Protein Pathway Activation by Epinephrine

What is effective signaling? Specificity? Sensitivity?

Page 9: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Adenylate Cyclase Activation/Deactivation

Page 10: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Cyclic AMP Deactivation

Page 11: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Protein Kinase A Activation by cAMP

Page 12: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Protein Kinase A Regulation by Phosphorylation

Dephosphorylation blocks substrate from active site

Catalytic subunit: light green

Activation loop: dark green

Substrate target protein: blue

Page 13: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

External Signal for G-Protein Activation

α-adreneric receptor is also activated by epinephrine and norepinephrine

IP3, a product of phosphatidylinositol bisphosphate hydrolysis signals a calcium influx and protein kinase C activation

Page 14: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Phosphoinositide Cascade

Page 15: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Calcium Binding Protein: Calmodulin

EF-hand protein familyExtended unbound form

Bent bound to a target protein

Ca+2 ions

Page 16: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Receptor Tyrosine Kinases

Operative for certain hormones and signaling molecules that regulate growth (e.g. insulin)

Ligand binding allows the receptor monomer to form a dimer unit with cytoplasmic kinase domain catalytically active

Page 17: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Insulin receptor

Insulin binding site

Insulin binding site

Extracellular region

Cell surface

α,β subunits: one in space-filling (red) and other in backbone-trace form (yellow)

Page 18: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Insulin Receptor Tyrosine Kinase Activation

Inactive form (blue)

Activation loop (dark blue)

Active form (green)

Activation loop (dark green)

Note:Activation loop swings out with Tyr phosphorylation

Page 19: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Ras- rat sarcoma virus

Ras Signal Transduction Pathway

Color coding: red inactive; green active

Page 20: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Ras Signal Transduction Pathway

Page 21: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Ras Signal Transduction Pathway

Protein phosphorylation can lead to subsequent gene activation

Page 22: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Lipid Hormone Signaling

Includes thyroid hormones that stimulate metabolism (right) as well as hormones for salt, water and reproductive functions

Do not bind to cell-surface receptors

Directly cross membranes to interact with intracellular receptors

Page 23: Caffeine Signaling via Ligand-Receptor Binding Agonist - ligand binding to a receptor and eliciting a response Antagonist - ligand binding to a receptor

Lipid Hormones: Eicosanoids

Regulation of blood pressure, blood coagulation, inflammation, pain and fever

Aspirin inhibits cyclooxygenase activity and therefore serve as a blood thinner


Statistical Thermodynamics: Ligand Binding - KinemageStatistical Thermodynamics: Ligand Binding Based on Cantor & Schimmel, Chapt. 15 LIGAND EQUILIBRIA Macroscopic and microscopic

of Discrete Receptor Flexibility in Ligand Docking Four ...ablab.ucsd.edu/pdf/09_4D_Bottegoni_JMC.pdfThe 4D docking method reproduced the correct ligand binding geometry in 77.3% of

Prediction of ligand binding sites

Nuclear receptor ligand-binding domains, looked at from all directions

Biomolecular Ligand-Receptor Binding Studies: Theory ... · What if the receptor/ligand system is more complicated than 1:1? 14 Multiple sites for a single ligand, Kd some for all

The importance of understanding ligand-binding sites in ... · Validated Targets Combinatorial Chemistry Libraries + = Ligand-Receptor Complexes THE “DOCKING ” PROBLEM Computed

Structure of the Glutamate-Like Receptor GLR3.2 ligand ... · The ligand-binding pocket of GLR3.2 LBD also resembles the ligand-binding pocket of iGluR LBDs (Figure 1c-d), with the

©Duane Sears Reversible Ligand Binding Reactions ... · Reversible Ligand Binding Reactions: Biological Significance and ... MONOVALENT equilibrium ligand ... Acetate Equilibrium

Kinetic analysis of ligand binding to interleukin-2 receptor

LIGAND-BINDING ASSAYS

Defining a canonical ligand-binding pocket in the orphan ... · Defining a canonical ligand-binding pocket in the orphan nuclear receptor Nurr1 Ian Mitchelle S. de Vera1,5,†, Paola

HTRF Ligand Binding Assay for the Chemokine Receptor CXCR4 · The chemokine receptor CXCR4 has multiple critical functions in normal physiologies including embryonic development of

G-protein-coupled receptor structure, ligand binding … · G-protein-coupled receptor structure, ligand binding and activation as ... spin interactions,

Regulation of type II interleukin-4 receptor assembly …...Regulation of type II interleukin-4 receptor assembly and signaling by ligand binding kinetics and affinities Dissertation

AMPA receptor ligand-binding domain: Site-directed ...ethesis.helsinki.fi/julkaisut/mat/bioti/vk/lampinen/amparece.pdf · agonist binding, leaving antagonist binding intact. This

Ligand Binding-Dependent Functions of the Lipocalin NLaz ...digital.csic.es/bitstream/10261/110964/1/Ligand Binding-Dependent.… · 1 Ligand Binding-Dependent Functions of the Lipocalin

Receptor Flexibility in de Novo Ligand Design and Dockingbrd/Teaching/Bio/asmb/current/Papers/jm... · Receptor Flexibility in de Novo Ligand ... binding-site flexibility into de

Alternate Glucocorticoid Receptor Ligand Binding Structures Influence Outcomes in An

Functional analysis of the ligand binding site of EGF-receptor

Chemomechanical mapping of ligand–receptor binding

Location of Ligand-binding Sites on the Nicotinic ... · Location of Ligand-binding Sites on the Nicotinic Acetylcholine Receptor &-Subunit* (Received for publication, February 21,

Determining Force Dependence of Two-Dimensional Receptor ... · Determining Force Dependence of Two-Dimensional Receptor-Ligand Binding Affinity by Centrifugation James W. Piper,*

DHVI Biomolecular Interaction Analysis (BIA) Core Facility · analyses of receptor-ligand interactions, including TCR-ligand and antibody-antigen binding, and HIV Envelope protein

Signal Transduction Lecture 14. Ligands & Receptors n Ligand l Neurotransmitters & drugs n Receptor proteins l ligand binds to multiple receptors n Binding

Measurement of Ligand–G Protein-coupled …...Although ligand–G protein-coupled receptor (GPCR) interactions can be quantified by observing the binding of a radiolabelled ligand

Adhesion of membranes via receptor–ligand complexes ... · Adhesion of membranes via receptor–ligand complexes: Domain formation, binding cooperativity, and active processes†

Kinetika receptor- ligand komplexov

PDZ Ligand Binding-Induced Conformational Coupling …bcz102.ust.hk/publications/2017/2017_JMB_PDZ Ligand... · PDZ Ligand Binding-Induced Conformational Coupling of ... Kowloon,

Biomolecular Ligand-Receptor Binding Studies: Theory, Practice

AMPA receptor ligand-binding domain: Site-directed mutagenesis

Ligand-receptor binding kinetics in surface plasmon ... binding kinetics in surface plasmon resonance cells: A Monte Carlo analysis Jacob Carroll1, Matthew Raum2, Kimberly Forsten-Williams3

Receptors and Drug Action · Antagonist: Affinity for receptor No intrinsic activity Partial agonist (later) Enzyme inhibitors. Binding of ligand to receptor •Covalent bond •Ionic

Influencing Receptor Ligand Binding Mechanisms with ... · Influencing Receptor-Ligand Binding Mechanisms with Multivalent Ligand Architecture Jason E. Gestwicki,† Christopher W

Allosteric binding site in a Cys-loop receptor ligand-binding domain

A NanoBRET-based binding assay for Smoothened allows real … · allows kinetic analysis of ligand-receptor binding in living HEK293 cells and competition binding experiments using