Week 28 / G-Protein-Coupled Receptor 1

Question 1

Q: What happens when an agonist drug binds to its receptor?

Answer 1

A: The drug-receptor (D-R) complex is formed, which undergoes a conformational change, triggering a series of biochemical processes inside the cell, leading to a biological response.

Question 2

Q: What is signal transduction?

Answer 2

A: Signal transduction, or receptor signalling, is the process through which the drug-receptor complex undergoes a conformational change and triggers a chain of biochemical events inside the cell, resulting in a biological response.

Question 3

Q: What is the signalling cascade or signal transduction pathway?

Answer 3

A: It is the chain of biochemical events triggered inside the cell after receptor signalling, leading to a biological response.

Question 4

Q: What is the first stage of the receptor signalling process?

Answer 4

A: Signal reception – the agonist drug binds to and activates a specific receptor on or inside the target cell.

Question 5

Q: What happens during the signal transduction stage?

Answer 5

A: The drug-receptor complex activates a series of relay proteins and produces second messengers inside the cell.

Question 6

Q: What is the final stage of receptor signalling?

Answer 6

A: Cellular response – a cellular or biological response is triggered as a result of the original drug binding signal.

Question 7

Q: What occurs during signal reception in receptor signalling?

Answer 7

A: The agonist drug binds to and activates a specific receptor on or inside the target cell.

Question 8

Q: What happens during the signal transduction stage of receptor signalling?

Answer 8

A: The drug-receptor complex activates a series of relay proteins and produces second messengers inside the cell.

Question 9

Q: What does the cellular response stage involve in receptor signalling?

Answer 9

A: A cellular or biological response is triggered as a result of the original drug binding signal.

Question 10

Q: What is the first major signal transduction pathway?

Answer 10

A: Activation of receptor-ion channels (Ligand-gated receptors).

Question 11

Q: What is the second major signal transduction pathway?

Answer 11

A: Activation of second messenger pathways via G-protein-coupled receptors.

Question 12

Q: What is the third major signal transduction pathway?

Answer 12

A: Activation of enzyme-linked receptors (e.g., Tyrosine kinase-linked receptors).

Question 13

Q: What is the fourth major signal transduction pathway?

Answer 13

A: Direct activation of gene transcription via intracellular receptors.

Question 14

Q: What is a receptor superfamily?

Answer 14

A: A group of receptors with a similar basic molecular structure that use the same signal transduction pathway.

Question 15

Q: What are the 4 major receptor superfamilies?

Answer 15

A:

Ligand-gated / Ion channel-linked receptors

G-protein-coupled receptors

Enzyme-linked / Kinase-linked receptors

Intracellular / Nuclear receptors.

Question 15

Q: What are G-protein-coupled receptors (GPCRs)?

Answer 15

A: A large and diverse superfamily of integral membrane proteins that convert extracellular signals into intracellular responses.

Question 16

Q: How many GPCRs are there in humans?

Answer 16

A: Approximately 800 members.

Question 17

Q: What do GPCRs regulate?

Answer 17

A: They regulate virtually every aspect of physiology and mediate responses to hormones, neurotransmitters, growth factors, as well as responses to vision, olfaction, and taste signals.

Question 18

Q: What is the common structural feature of GPCRs?

Answer 18

A: They share a common structural motif of seven transmembrane (7-TM) α-helices.

Question 19

Q: What happens when an agonist binds to a GPCR?

Answer 19

A: It activates cytoplasmic heterotrimeric G-proteins, which modulate downstream effector proteins, leading to a biological response.

Question 20

Q: What are the three key regions of a GPCR?

Answer 20

A: The extracellular region, the transmembrane (TM) region, and the intracellular region.

Question 21

Q: What role do -arrestins play in GPCR signaling?

Answer 21

A: They couple to GPCRs and lead to either receptor desensitization and internalization or activation of downstream effector proteins, resulting in a biological response.

Question 22

Q: What is the function of the extracellular region of a GPCR?

Answer 22

A: It modulates ligand access to the binding site on the receptor.

Question 23

Q: What does the transmembrane (TM) region of a GPCR consist of?

Answer 23

A: Seven transmembrane (7-TM) α-helices (TM1-TM7), which form the structural core, bind ligands, and transduce this information to the intracellular regions.

Question 24

Q: What is the role of the intracellular region of a GPCR?

Answer 24

A: It interfaces with cytosolic signaling proteins, such as G-proteins.

Question 25

Q: What is the key feature of GPCRs?

Answer 25

A: Their interaction with heterotrimeric GTP-binding proteins (G-proteins).

Question 26

Q: What is the role of heterotrimeric G-proteins in GPCR signaling?

Answer 26

A: They play a pivotal role in signal-transduction pathways by conveying signals from the cell-surface GPCR to downstream intracellular effector proteins.

Question 27

Q: Where are heterotrimeric G-proteins localized in the cell?

Answer 27

A: They are localized at the inner leaflet of the plasma membrane.

Question 28

Q: How do heterotrimeric G-proteins act in signal transduction?

Answer 28

A: They act as molecular binary switches, translating agonist GPCR binding into modulation of the activity of downstream intracellular effector proteins, resulting in a biological response.

Question 29

Q: What are heterotrimeric G-proteins composed of?

Answer 29

A: They are composed of three different protein subunits: α, β, and γ.

Question 30

Q: Functionally, what units do heterotrimeric G-proteins consist of?

Answer 30

A: Functionally, they consist of the α subunit (Ga) and a tightly associated βγ complex.

Question 31

Q: What is the role of the lipid extensions of the Go and Gy subunits in heterotrimeric G-proteins?

Answer 31

A: The lipid extensions bind and tether the G-protein complex to the plasma membrane.

Question 32

Q: What nucleotide is bound to the Ga subunit of heterotrimeric G-proteins in the inactive (resting) state?

Answer 32

A: GDP is bound to the Ga subunit in the inactive (resting) state.

Question 33

Q: How many Ga, Gß, and Gy subunits/isoforms have been identified in the human genome?

Answer 33

A: 21 Ga, 5 Gß, and 12 Gy subunits/isoforms have been identified. This allows for multiple permutations of distinct heterotrimeric complexes.

Question 34

Q: What is located between the two domains of the Ga subunit in its GDP-bound resting state?

Answer 34

A: A nucleotide-binding pocket is located between the two domains.

Question 35

Q: What activity is associated with the Ras-like domain of the Ga subunit?

Answer 35

A: The Ras-like domain has GTPase activity, which hydrolyzes GTP to GDP.

Question 36

Q: What are the two domains that compose the Ga subunit?

Answer 36

A: The Ga subunit is composed of the Ras-like domain and an α-helical domain.

Question 36

Q: What provides binding sites for the Gβγ subunits in the Ga subunit?

Answer 36

A: The Ras-like domain of the Ga subunit provides binding sites for the Gβγ subunits.

Question 37

Q: What modifications occur to the N-terminus of the Ga subunit, and what is their function?

Answer 37

A: The N-terminus of the Ga subunit is either myristoylated or palmitoylated, which results in the attachment of the G-protein to the plasma membrane.

Question 38

Q: What happens when an agonist binds to a GPCR?

Answer 38

A: It causes a conformational change in the receptor, which leads to the exchange of GDP for GTP on the Ga subunit.

Question 39

Q: What occurs after the Ga-GTP subunit dissociates from the Gβγ dimer?

Answer 39

A: Both Ga-GTP and the freed Gβγ proceed to interact with and regulate the activity of unique downstream effector proteins, resulting in a biological response.

Question 40

Q: How is the G-protein deactivated after signaling?

Answer 40

A: The GTPase activity of the Ga subunit hydrolyzes GTP to GDP, returning the G-protein to the inactive resting state.

Question 41

Q: What accelerates the hydrolysis of GTP to GDP in the Ga subunit?

Answer 41

A: The hydrolysis of GTP to GDP is accelerated by Regulators of G-protein Signaling (RGS) or GTPase-accelerating proteins (GAPs).

Question 42

Q: What happens after the Ga-GDP re-assembles with the Gβγ dimer?

Answer 42

A: The Ga-GDP re-assembles with the Gβγ dimer to form the inactive G-protein.

Question 43

Q: How are G-proteins classified?

Answer 43

A: G-proteins are classified based on their Ga subunits into four families: Gas, Gai, Ga/11, and Go 2/13.

Question 44

Q: What is the function of the Gas family of Ga proteins?

Answer 44

A: The Gas family stimulates adenylate cyclase, which increases cAMP levels.

Question 45

Q: What does the Go 2/13 family of Ga proteins activate?

Answer 45

A: The Go 2/13 family activates the Rho family of GTPases.

Question 46

Q: What does the Go/11 family of Ga proteins activate?

Answer 46

A: The Go/11 family stimulates phospholipase C-B, leading to the production of IP3 and DAG.

Question 47

Q: What is the function of the Gai family of Ga proteins?

Answer 47

A: The Gai family inhibits adenylate cyclase, which decreases cAMP levels.

Question 48

Q: How do Gα proteins mediate GPCR signalling?

Answer 48

A: Gα proteins regulate the levels of intracellular second messengers, which in turn regulate downstream effector proteins, resulting in a biological response.

Question 49

Q: What are the key second messengers in Gα-mediated signalling pathways?

Answer 49

A: Key second messengers include cAMP, IP3, and Ca²⁺.

Question 50

Q: What does Gαs-GTP activate in the cAMP signalling pathway?

Answer 50

A: Gαs-GTP activates Adenylyl Cyclase (AC), which increases cAMP levels.

Question 51

Q: What does Gαi/o-GTP do in the cAMP signalling pathway?

Answer 51

A: Gαi/o-GTP inhibits Adenylyl Cyclase (AC), leading to a decrease in cAMP levels.

Question 52

Q: What happens in the Inositol 1,4,5-trisphosphate (IP3)/calcium signalling pathway?

Answer 52

A: Gαq/11-GTP activates Phospholipase Cβ (PLCβ), which increases IP3 and DAG, leading to an increase in Ca²⁺.