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Chapter 5. Detection of Extracellular signals: the role of receptors. Objectives. What are the main types of receptors How to those receptors function in general Why is ligand binding important How do we measure ligand binding. Role of the Receptor. Specificity, only one signal detected - PowerPoint PPT Presentation
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Chapter 5
Detection of Extracellular signals: the role of receptors
Objectives
• What are the main types of receptors• How to those receptors function in general• Why is ligand binding important• How do we measure ligand binding
Role of the Receptor
• Specificity, only one signal detected• High affinity, usually low concentrations 10-8 M• Must propagate message• Must turn off
Types of Receptors - G-protein Coupled Receptors
Gγ
Gβ Gα
Signal propagation
Signal propagation
Extracellular
Intracellular
–P P–
Types of Receptors – Enzyme Activity
Extracellular
Intracellular
Types of Receptors – Ligand Gated Channel
Extracellular
Intracellular
acetylcholine
sodium
GCPR
β2 Adrenergic Receptor
GPCR
• 7 Transmembrane helices• Signal through heterotrimeric G-proteins or
associated proteins• Mediate signaling for hormones,
neuropeptides, light, smell, and taste• Can involve phosphorylation
Ligand Gated Receptors
• Usually 5 membrane helices• Create a channel for ions• Rapid open / close• Function in neuronal
signaling
Enzyme Receptors
• Largest Group Receptor Tyrosine Kinases– Autophosphorylation– Dimers to be active
• Some Receptors phosphorylate other proteins
Intracellular Receptors
NPC
Hsp56
Hsp70
Hsp90
PromotorDNA
Nucleus
Cytosol
Extracellular
Ligand binding to Receptors
• Agonist – ligand that binds and activates a receptor
• Antagonist – ligand that binds receptor but does not activate it
• Constitutively Active – a receptor that is active in the absence of ligand
• Consider Ligand/Receptor binding as very similar to Ligand/Protein binding
Ligand binding to Receptors
Equations:
Ligand binding to Receptors
• How to measure [LR]– Fluorescence labeling
• Hard to quantify– Radioisotope
• 131I, 125I, 3H– Influences
• Time, pH, temperature, other ligands present…
Ligand binding to Receptors
• How much ligand binds nonspecifically– Compete with
unlabeled ligand– Subtract
• Kd
Total binding
Specific binding
Nonspecific binding
Scatchard Plot
Plot: vs
Scatchard Plots
Receptor Sensitivity
• Receptor Density– More receptors = better chance of detection– Less receptors = desensitization
• Clathrin coated vesicles and endocytosis
• Refractory Response– Homologous desensitization– Heterologous desensitization
Homologous desensitization