Lecture 17. G Protein-Coupled Receptors

Question 1

What do all G-protein coupled receptors share?

Answer 1

The same basic structure
Extracellular domains (E1 and loops E2-4)
Trans-membrane domains (TM1-7)
Cytosolic domains (C1-C3 and a C4 tail)

Question 2

What does ligand binding cause in G-proteins?

Answer 2

Alteration the conformation of the TM domains, and reveals amino acids in the cytosolic domains for activating heterotrimeric G-proteins

Question 3

What can bulky ligands (proteins and peptides) also bind to?

Answer 3

Extracellular loops of the N-terminus

Question 4

What is the heterotrimeric G-protein?

Answer 4

A trimer of α, β, and γ subunits (Gα, Gβ, and Gγ) that is inactive when bound to GDP (or alternatively, no guanine nucleotide) but active when bound to GTP

Question 5

What is the GTP hydrolysis activity of Gα?

Answer 5

Slow

Question 6

How many Gα, Gβ, and Gγ subunits do mammalian cells contain?

Answer 6

Have at least 20 Gα subunits
Have at least 5 Gβ subunits
Have at least 12 Gγ subunits

Question 7

What does Gs mean?

Answer 7

Stimulates adenylate cyclase

Question 8

What are examples of Gs?

Answer 8

Glucagon, epinephrine

Question 9

What does Gi mean?

Answer 9

Inhibits adenylate cyclase

Question 10

What are examples of Gi?

Answer 10

Adenosine, prostaglandin

Question 11

What is the fight for flight response?

Answer 11

A very rapid response (acute stress response) to a perceived harmful event, an attack or a threat to survival

Question 12

What stimulates the fight or flight response?

Answer 12

Epinephrine (adrenaline) and cortisol from the adrenal glands

Question 13

How does cortisol affect the body?

Answer 13

Increases blood sugar through gluconeogenesis
Suppresses the immune system

Question 14

How does epinephrine affect the body?

Answer 14

A hormone and a neurotransmitter that acts on nearly all body tissues
Binds a variety of adrenergic receptors (major subtypes α₁, α₂, β₁, β₂, β₃
Adrenergic receptors are GPCRs:
Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis in muscle
Binding to β-adrenergic receptors triggers glucagon secretion in the pancreas, and increased lipolysis by adipose tissue

Question 15

What is cAMP?

Answer 15

A second messanger
It is used as a signalling molecule in all cells
It activates a variety of proteins

Question 16

What mediates the affect of cAMP?

Answer 16

Protein kinase A (PKA)

Question 17

What does activated PKA target and phosphorylate?

Answer 17

Transcription factors
Ion channels
A variety of other enzymes

Question 18

What are GPCRs?

Answer 18

The largest class of cell-receptors