3.1

Question 1

What are GPCRs?

Answer 1

The largest group of cell surface receptors involved in numerous physiological processes.

Question 2

How many GPCR genes exist in humans?

Answer 2

Over 800, accounting for ~2% of the genome.

Question 3

What physiological processes involve GPCRs?

Answer 3

Neurological, endocrine, immunological, olfaction, light perception, embryogenesis.

Question 4

What percentage of drugs target GPCRs?

Answer 4

Around 30%.

Question 5

Describe the basic topology of a GPCR.

Answer 5

7 transmembrane α-helices, extracellular N-terminus, cytoplasmic C-terminus, and 6 loops (3 ECLs and 3 ICLs).

Question 6

What is conserved in GPCR structure?

Answer 6

Core TM domain motifs; variable N- and C-termini.

Question 7

Where are key sequence motifs usually located?

Answer 7

Within the transmembrane helices.

Question 8

What types of stimuli do GPCRs detect?

Answer 8

Photons, odorants, taste ligands, peptides, lipids, nucleotides.

Question 9

What are orphan GPCRs?

Answer 9

Receptors with no known endogenous ligand (~120 currently known).

Question 10

Why are orphan GPCRs important?

Answer 10

Potential targets for drug discovery.

Question 11

What are the five main GPCR families?

Answer 11

Rhodopsin (A), Secretin (B), Glutamate (C), Adhesion, Frizzled (F).

Question 12

Which family is the largest?

Answer 12

Rhodopsin (Class A) – ~700 members, ~90% of all GPCRs.

Question 13

What are ligands for Class A GPCRs?

Answer 13

Small molecules, neurotransmitters, peptides, olfactory/visual/taste ligands.

Question 14

What are conserved motifs in Class A GPCRs?

Answer 14

DRY motif (TM3), NPxxY (TM7), Pro in TMs 5–7, Trp in TM6, Cys-Cys bridge, palmitoylation in C-tail.

Question 15

What ligands activate Class B GPCRs?

Answer 15

Polypeptide hormones (e.g. glucagon, secretin, VIP, CRH).

Question 16

What structural features define Class B GPCRs?

Answer 16

Large N-terminus with Cys-Cys bridges, Pro residues in TMs 4–6, NPGQ motif.

Question 17

What receptors belong to Class C?

Answer 17

Metabotropic glutamate receptors, GABA_B, CASR, sweet/umami taste receptors.

Question 18

What is the Venus Flytrap domain?

Answer 18

A large N-terminal ligand-binding domain unique to Class C GPCRs.

Question 19

How do Class C GPCRs exist structurally?

Answer 19

As obligate dimers (homomers or heteromers).

Question 20

What is a unique feature of Adhesion GPCRs?

Answer 20

They have a GPCR proteolysis site (GPS) cleaved from the 7TM domain.

Question 21

What do Adhesion GPCRs bind?

Answer 21

Extracellular matrix proteins.

Question 22

Are Adhesion GPCRs well characterised?

Answer 22

No – many are orphan receptors.

Question 23

What activates Frizzled receptors?

Answer 23

Wnt proteins (lipoglycoproteins).

Question 24

What is the role of Smoothened (SMO)?

Answer 24

Activated indirectly by Hedgehog (HH) via proteins acting on PTCH.

TM protein patched

Question 25

What are G proteins?

Answer 25

Heterotrimeric proteins (Gα, Gβ, Gγ) that mediate GPCR signalling.

Question 26

What does the Gα subunit do?

Answer 26

Binds GDP/GTP and interacts with effectors.

Question 27

What is the role of Gβγ?

Answer 27

Remains together; regulates ion channels and some signalling enzymes.

Question 28

Describe the activation of G proteins.

Answer 28

Ligand binding → GPCR activates Gα (GDP → GTP) → Gα dissociates from Gβγ → both activate effectors.

Question 29

How is the signal terminated?

Answer 29

Gα hydrolyses GTP to GDP → rebinds Gβγ.

Question 30

What proteins regulate G protein activity?

Answer 30

GAPs (accelerate inactivation), GEFs (accelerate activation).

Question 31

What determines signalling specificity?

Answer 31

Different combinations of GPCR, G protein, and effector components.

Question 32

What does Gαs do?

Answer 32

Activates adenylyl cyclase → ↑cAMP.

Question 33

What does Gαi do?

Answer 33

Inhibits adenylyl cyclase → ↓cAMP.

Question 34

What does Gαq activate?

Answer 34

Phospholipase Cβ (PLCβ).

Question 35

What does PLCβ produce?

Answer 35

IP₃ (releases Ca²⁺) and DAG (activates PKC).

Question 36

Describe Gβγ's role in heart rate.

Answer 36

Muscarinic ACh receptor → Gβγ opens K⁺ channel → hyperpolarisation → slower heart rate.

Question 37

How is GPCR signalling amplified?

Answer 37

One ligand → many G proteins → many second messengers.

Question 38

Why is this efficient?

Answer 38

Few receptors needed to generate large cellular responses.

Question 39

What enzyme phosphorylates active GPCRs?

Answer 39

GPCR kinases (GRKs).

Question 40

What proteins bind phosphorylated GPCRs?

Answer 40

Arrestins (visual: arrestin-1, -4; non-visual: β-arrestin1, 2).

Question 41

What are the main roles of arrestins?

Answer 41

Desensitisation (uncoupling from G proteins), endocytosis initiation, alternative signalling (e.g., MAPK).

Question 42

How does arrestin desensitise GPCRs?

Answer 42

Uncouples the receptor by sterically hindering access to binding domains.

Question 43

What happens after GPCR internalisation?

Answer 43

Receptors can be recycled or degraded depending on cell signalling context.

Question 44

Which statement is true about arrestins?

Answer 44

C. Arrestin binding initiates GPCR internalisation.