GPCRs and G-Protein Signaling Quiz

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Questions and Answers

Which amino acids can serve as phosphorylation sites in receptors identified in Class-A GPCRs?

Lysine and Methionine

Aspartic Acid and Glutamic Acid

Serine and Threonine (correct)

Alanine and Glycine

What is a characteristic feature of Class-C GPCRs?

Single polymeric structure

Formation of obligatory dimers (correct)

Presence of a dual operating mechanism

Lack of a transmembrane domain

What structural domains are found in Class-C GPCRs?

Nuclear localization sequence and helix-turn-helix

Venus flytrap domain and cysteine-rich domain (correct)

Transmembrane domain and lipid-binding domain

Signal peptide and coiled-coil domain

Which of the following describes the composition of G-proteins?

Composed of three different subunits Signup and view all the answers

In Class-A GPCRs, which amino acid site is notable for palmitoylation?

Cysteine Signup and view all the answers

What is the primary function of Gs proteins?

Stimulate adenylyl cyclase to increase cAMP Signup and view all the answers

Which proteins act on Ga to regulate G protein signaling?

RGS proteins Signup and view all the answers

Which family of G proteins is associated with inhibiting adenylyl cyclase?

Gi proteins Signup and view all the answers

What is the result of G protein activation by an agonist?

GDP dissociates from G proteins Signup and view all the answers

Which second messenger is produced as a result of Gq protein activation?

DAG Signup and view all the answers

What is a primary characteristic of Class-B GPCRs?

They possess a very large N-terminus consisting of 200-2800 amino acids. Signup and view all the answers

Which of the following is considered a GPCR ligand?

Thyroid-stimulating hormone Signup and view all the answers

What is the main role of G proteins in GPCR signaling?

To couple the receptor activity to downstream signaling pathways. Signup and view all the answers

Which class of GPCR is known for having receptors related to fungal pheromones?

Class-D Signup and view all the answers

In terms of structural features, what do all GPCRs share?

Seven lipophilic transmembrane helical domains. Signup and view all the answers

Which statement correctly describes the nomenclature of GPCRs?

GPCR stands for G-Proteins Coupled Receptors. Signup and view all the answers

What physiological function can GPCRs regulate?

Major cell signaling systems. Signup and view all the answers

Which of these GPCR classes is still considered controversial?

Class-F Signup and view all the answers

What is the primary effect of catecholamine interaction with ß3AR?

Stimulation of adenylyl cyclase and PKA Signup and view all the answers

What physiological response is associated with the activation of alpha1 adrenergic receptors?

Vasoconstriction Signup and view all the answers

Which adrenergic receptor is most likely to cause a decrease in cyclic AMP levels when activated?

Alpha2 (a2) Signup and view all the answers

What is a potential therapeutic use of BRL37344?

Treatment of obesity Signup and view all the answers

Which sequence of events occurs after G-protein activation of phospholipase C in alpha1 adrenergic signaling?

Activation of DAG and Ca2+ release Signup and view all the answers

What is the primary substrate of phospholipase C (PLC)?

Phosphatidic acid Signup and view all the answers

Which family of proteins is regulated by GPCRs involving PLC-b?

Phospholipases Signup and view all the answers

What initiates the activation of PLC by Gq?

Gqa-GTP binding to PLC-b Signup and view all the answers

Which of the following components is required for the activation of PKC?

Calcium and DAG Signup and view all the answers

Which process contributes to the desensitization of GPCRs following activation?

Internalization through clatherin-coated pits Signup and view all the answers

What role do GPCR kinases (GRKs) play in the regulation of GPCRs?

They are responsible for down-regulation of GPCRs Signup and view all the answers

Which of the following statements is true regarding the activation of enzymes downstream of PLC?

Calcium and DAG stimulate PKC activation. Signup and view all the answers

What is a characteristic of homologous desensitization in GPCRs?

It involves GRKs and arrestins. Signup and view all the answers

What is the primary effect of stimulating b1 adrenergic receptors in the heart?

Increased force and velocity of heart contraction Signup and view all the answers

Which adrenergic receptor is primarily involved in smooth muscle relaxation in the lungs?

b2 adrenergic receptors Signup and view all the answers

What is the mechanism of action for b2-selective agonists like Salbutamol in treating asthma?

Cause smooth muscle relaxation Signup and view all the answers

What is the main function of b3 adrenergic receptors in adipocytes?

Regulate lipolysis Signup and view all the answers

Which of the following drugs is a selective b1 adrenergic receptor antagonist?

Metoprolol Signup and view all the answers

What is not a typical outcome of b1 adrenergic receptor stimulation?

Decreased myocyte relaxation rate Signup and view all the answers

What differentiates Salmeterol from Salbutamol in terms of usage?

Longer duration of action Signup and view all the answers

Which receptor is associated with the treatment of angina and hypertension?

b1 and b2 adrenergic receptors Signup and view all the answers

Study Notes

Introduction to G Protein-Coupled Receptor Signal Transduction

G protein-coupled receptors (GPCRs) are a large family of transmembrane receptors that play crucial roles in cell signaling.
GPCRs are involved in diverse physiological processes and are prominent drug targets.
Key components of a GPCR system include orthosteric sites, G-proteins, and intracellular signaling cascades.

G Protein-Coupled Receptors and their Signaling Systems

This section aims to familiarize students with the components of the GPCR system, understand how these receptors become activated, and provide examples of systems regulated by GPCRs.
It also touches upon physiological and pharmacological aspects.

Major Players Covered in PCL302

Orthosteric sites are crucial for endogenous ligand binding, where many GPCR drugs bind.
G protein-coupled receptor (GPCR) internalization and desensitization blocks G protein access.
Additional signaling cascades are activated following receptor activation.

GPCRs are encoded by hundreds of human genes

The number of GPCRs varies between mice and humans.
Various groups of GPCRs exist (e.g., Rhodopsin, Frizzled, Taste Type 2, Secretin, Olfactory, etc).
Data shows significant numbers of GPCRs encoded in both species.

GPCR Superfamily

GPCRs are categorized into families based on their structures and function.
A diagram showcases the relationships between different GPCR families.

GPCR Ligands

Neurotransmitters like adrenaline, dopamine, serotonin, and glutamate, as well as GABA, are ligands.
Peptide hormones (e.g., thyroid-stimulating hormone, parathyroid hormone) are also ligands.
Sensory stimuli, like light, odors, salt, and sugar, can act as ligands.
Prostaglandins and glycoprotein growth-differentiation factors are other categories of GPCR ligands.

GRVFS classification of vertebrate GPCR

The presented table classifies GPCRs based on their characteristics and provides example receptors for each family.

Nomenclature

GPCR stands for G-protein coupled receptors, a broad term.
7TM refers to the seven transmembrane domains found in many GPCR types.

GPCRs are major drug targets

GPCRs are major targets for both protein and small molecule drugs.
The relative proportions of drug targets for each category of GPCR are presented graphically.

Structural Features of GPCRs

GPCRs comprise seven transmembrane domains, extracellular and intracellular loops, and terminal regions.
Ligand binding occurs within or outside the transmembrane helices.
G proteins interact with the inside surface of the receptor.

Secondary Structure (Class-A)

The structure of GPCRs, particularly for Class-A receptor types (e.g. dopamine receptors), are depicted.
Different features such as locations of glycosylation sites, palmitoylation sites, and phosphorylation sites are indicated.

Secondary Structure (β-adrenergic receptor)

A diagram of a specific class-A GPCR, the beta-adrenergic receptor.

Class-B: Secretin Receptor

The structure of a Secretin receptor is depicted, showing details like alpha and beta sheets and ligand-binding motifs.

Class-C: Metabotropic Glutamate Receptor

The structural features of a Metabotropic receptor, highlighting important domains like glutamate binding site and the seven-transmembrane region.

Homomers Heterodimers of Class C GPCRs

Illustrates the dimeric nature of some class C GPCRs.

G-Proteins, Heterotrimeric G protein structure

Shows the structure of G-proteins—heterotrimeric components with alpha, beta, and gamma subunits.

G Protein-Coupled Receptor (GPCR) Mechanism

Describes the general mechanism of GPCR signaling, which begins with ligand binding.

Inactivation of G Proteins

Focuses on GTP hydrolysis as a crucial part of deactivating G proteins.

Regulators of G protein Signaling (RGS Proteins)

RGS proteins—regulators of G protein signaling are highlighted in their function and classification.

Regional expression patterns and known transcriptional modulators of CNS-relevant RGS genes

A table that details CNS expression patterns and potential modulators.

G protein deactivation by RGS

Diagrams on G-protein deactivation using RGS proteins

The Family of Heterotrimeric G Proteins

Shows the classification of heterotrimeric G proteins into families (e.g. Gs, Gi, Gq, G12).

G βy Subunits

Presents a table detailing the various subunit types.

Effectors Regulated by G proteins, Adenylyl Cyclase

Displays adenyl cyclase enzymes and their catalytic domains.
Includes details on adenyl cyclase isoforms, activators, and inhibitors.

Gs and Gi Regulation of Adenylyl Cyclase

Explains how Gs and Gi proteins regulate adenylyl cyclase activity.
Includes diagrams illustrating the interactions

cAMP Signaling

Outlines how cAMP regulates cellular processes through PKA activation.

Examples of cAMP-regulated systems

Provides examples where cAMP-related mechanisms mediate specific biological responses.

Effectors Regulated by G proteins, PLC-β

Discusses the role of PLC-β as an effector regulated by G proteins.

Inositol Phosphates

Diagrams the inositol phosphate cycle pathway and related structures.

Stimulation of PLC by Gq

Describes how Gq proteins regulate PLC-β activity, emphasizing the hydrolysis of PIP2 to IP3 and DAG.

Down-stream of PLC

Details downstream effects of PLC including calcium stimulation and kinases.

PKC Family

Presents structural aspects and activators.

Adenylyl Cyclase

Demonstrates a visual representation of adenylyl cyclase regulation.

PLC

Outlines the steps related to PLC activation.

Ion Channels

Explains the basic mechanism that GPCRs have in relation to the regulation of ion channels.

GPCR Desensitization

Explains how G-protein coupled receptors (GPCRs) are regulated following activation, particularly the inactivation mechanisms involved.

Homologous Desensitization and Down-regulation of GPCRs

Discusses homologous desensitization and down-regulation of GPCRs.

GPCR Kinases (GRKs)

Details GPCR Kinases (GRKs) including their structures and domains.

Putative domain architecture of the (beta)-arrestins

Details the architecture of beta-arrestins.

Beta Arrestin as signaling effectors

Outlines how beta-arrestins function and are involved in different cellular processes.

Multiplicité d'action des GPCRs

Contains information on the multiple roles and signaling pathways of GPCRs.

D2-class responding neurons

Discusses the example of a signaling network of dopamine D2 receptors.

Multidimensional Drug efficacy

Explains how different criteria can be used to evaluate drug efficacy.

Heart Rate Regulation by Beta-Adrenergic Receptors

This section provides specifics about how Beta-adrenergic receptors influence heart rate, including the involved components and mechanisms.

𝛽–Adrenergic Receptor Antagonists

Lists drugs categorized as beta-adrenergic antagonists, along with their corresponding receptors and uses.

asthma

Discusses information related to asthma including prevalence among children.

𝛽2- Selective Receptor Agonists

Details specific agonists used in asthma treatment.

𝛽3 Adrenergic Receptors Regulation of Lipolysis

Explains the role of 𝛽3 adrenergic receptors in regulating lipolysis in adipocytes.

𝛽3-Selective Agonist

Describes the impact of a specific 𝛽3 selective agonist, BRL37344.

GPCRs That Stimulate Phospholipase C Activity: α1-Adrenergic Receptors.

Discusses how a1-adrenergic receptors influence smooth muscle via phospholipase C activation.

Agonists of Adrenergic Receptors

Shows agonists for different adrenergic receptors and their corresponding messengers and G proteins.

Effects of epinephrine on blood vessel caliber

Explains the effects of epinephrine on blood vessel caliber, including the role of different adrenergic receptors in different conditions.

Effect of Catecholamines on Vascular Smooth Muscle

Describes how epinephrine concentration dictates whether it causes vasoconstriction or vasodilation.

α1 Receptor Agonists

Discusses specific alpha-1 receptor agonists and their usage.

Adrenergic Receptors Drug List

Provides a summary list of adrenergic receptor-related drugs.

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Description

Test your knowledge on the characteristics and functions of G-protein coupled receptors (GPCRs), including Class-A, Class-B, and Class-C. This quiz covers aspects such as phosphorylation sites, structural domains, and the role of G-proteins in signaling. Perfect for students and professionals in biochemistry and pharmacology.