GPCRs

Question 1

Q2. Approximately what percentage of drugs on the market target GPCRs?
A. 10%
B. 25%
C. 50%
D. 75%
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Answer 1

✅ Answer: C. 50%

Question 2

Q1. GPCRs are involved in all of the following physiological processes EXCEPT:
A. Vision
B. Immune response
C. DNA replication
D. Mood regulation

Answer 2

✅ Answer: C. DNA replication

Question 3

Q3. Orphan receptors are GPCRs that:
A. Have no known function
B. Lack transmembrane domains
C. Do not couple to G proteins
D. Have no known endogenous ligand
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Answer 3

✅ Answer: D. Have no known endogenous ligand

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Question 4

Q4. Which GPCR class is the largest and includes the β2-adrenergic receptor?
A. Class B
B. Class C
C. Class A (Rhodopsin family)
D. Class F

Answer 4

✅ Answer: C. Class A (Rhodopsin family)

Question 5

Q5. Which class of GPCRs is typically a dimer and contains a Venus flytrap domain?
A. Class A
B. Class B
C. Class C
D. Class F

Answer 5

✅ Answer: C. Class C

Question 6

Q6. Which GPCR class includes the frizzled and taste receptors?
A. Class A
B. Class B
C. Class C
D. Class F

Answer 6

✅ Answer: D. Class F

Question 7

Q7. What strategy was used to stabilize the β2AR for crystallization at 3.7 Å resolution?
A. Nanobody binding
B. Lipid bilayer reconstitution
C. Monoclonal antibody binding (Fab5)
D. Ligand crosslinking

Answer 7

✅ Answer: C. Monoclonal antibody binding (Fab5)

Question 8

Q8. What was inserted into the β2AR to help crystallize it at higher resolution (2.4 Å)?
A. Nanobody Nb80
B. GFP
C. T4 lysozyme
D. Fab5 fragment

Answer 8

✅ Answer: C. T4 lysozyme

Question 9

Q9. Which structural movement is characteristic of the active state of β2AR?
A. TM1 inward movement
B. TM5 shortening
C. TM6 outward movement
D. TM4 rotation

Answer 9

✅ Answer: C. TM6 outward movement

Question 10

Q10. What key change occurs in the ligand binding pocket during activation of β2AR?
A. Ligand leaves the pocket
B. Binding site collapses
C. Subtle side-chain rearrangements initiate conformational changes
D. New alpha helix is formed

Answer 10

✅ Answer: C. Subtle side-chain rearrangements initiate conformational changes

Question 11

Q11. What technique was used to prevent dissociation of the β2AR-Gs complex during crystallization?
A. Freeze-drying
B. T4 lysozyme fusion
C. Chemical crosslinking and nanobody Nb35
D. Electroporation

Answer 11

✅ Answer: C. Chemical crosslinking and nanobody Nb35

Question 12

Q12. Which part of the G protein does β2AR primarily interact with?
A. Gβ subunit
B. Gγ subunit
C. Gαs subunit (α5 helix, β3 strand, α4 helix)
D. Gαi subunit

Answer 12

✅ Answer: C. Gαs subunit (α5 helix, β3 strand, α4 helix)

Question 13

Q13. Which of the following statements about β2AR-G protein interaction is TRUE?
A. There are direct contacts between β2AR and Gβγ
B. ICL2 and TM5-TM6 of β2AR form the main interface with Gαs
C. GTP binding causes TM6 to move inward
D. Fab5 was used to stabilize the G protein complex

Answer 13

✅ Answer: B. ICL2 and TM5-TM6 of β2AR form the main interface with Gαs

Question 14

Q14. What does the α-helical domain (GαsAH) of Gαs do during activation?
A. Blocks the GTP site
B. Prevents dimerization
C. Flips down to stabilize GTP-bound form
D. Activates GPCR kinase

Answer 14

✅ Answer: C. Flips down to stabilize GTP-bound form

Question 15

Q15. Which of the following is a reason why GPCRs can mediate such a diverse range of functions?
A. They form covalent bonds with ligands
B. They all couple only to Gαs
C. They have different intracellular loop regions and ligand-binding domains
D. They only function in the central nervous system

Answer 15

✅ Answer: C. They have different intracellular loop regions and ligand-binding domains

Question 16

Q16. What makes GPCRs a major target in drug development?
A. Their intracellular location
B. Their involvement in genetic inheritance
C. Their role in a broad range of physiological processes
D. Their ability to form permanent complexes with DNA

Answer 16

✅ Answer: C. Their role in a broad range of physiological processes

Question 17

Q17. What happens immediately after ligand binding to a GPCR?
A. The receptor is internalized
B. GDP is hydrolyzed to GTP
C. The G protein is recruited and activated
D. The β and γ subunits are degraded

Answer 17

✅ Answer: C. The G protein is recruited and activated

Question 18

Q18. Which G protein pathway leads to activation of phospholipase C (PLC)?
A. Gαs
B. Gαi
C. Gαq
D. Gαt

Answer 18

✅ Answer: C. Gαq

Question 19

Q19. Which subunits can activate downstream effectors in GPCR signalling?
A. Only the α subunit
B. Only the γ subunit
C. Only the β subunit
D. Both α and βγ subunits

Answer 19

✅ Answer: D. Both α and βγ subunits

Question 20

Q20. Which conformational change marks the transition from inactive to active β2AR?
A. Collapse of the binding pocket
B. Straightening of TM1
C. Outward movement of TM6
D. Inward rotation of the α5 helix of Gα

Answer 20

✅ Answer: C. Outward movement of TM6

Question 21

Q21. The β2AR is crystallized in its inactive form using which type of ligand?
A. Inverse agonist
B. Full agonist
C. Neutral antagonist
D. Allosteric enhancer

Answer 21

✅ Answer: A. Inverse agonist

Question 22

Q22. What structural role did T4 lysozyme play in β2AR crystallization?
A. Acted as a fluorescent tag
B. Blocked ligand binding
C. Replaced flexible IL3 to stabilize the structure
D. Activated the receptor

Answer 22

✅ Answer: C. Replaced flexible IL3 to stabilize the structure

Question 23

Q1. Which feature of GPCRs contributes most significantly to their ability to regulate diverse physiological processes?
A. They all bind the same G protein
B. They function as tetramers
C. They couple to multiple types of intracellular effectors
D. They are limited to endocrine signalling
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Answer 23

✅ Answer: C. They couple to multiple types of intracellular effectors

Question 24

Q2. What accounts for the functional diversity observed within Class A GPCRs?
A. Their cytoplasmic tails are enzymatically active
B. Their N-terminal domains bind ATP
C. Structural diversity in the ligand-binding pocket
D. They only couple to Gαi

Answer 24

✅ Answer: C. Structural diversity in the ligand-binding pocket

Question 25

Q3. GPCR oligomerization, as seen in μ-opioid receptors, is functionally relevant because: A. It allows GPCRs to form voltage-gated pores B. It permits internalization via endocytosis C. It modifies ligand binding and signalling specificity D. It restricts GPCR expression to neurons

Answer 25

✅ Answer: C. It modifies ligand binding and signalling specificity

Question 26

Q4. Which of the following correctly matches the GPCR class with a structural or functional trait? A. Class A – long N-terminal domain B. Class B – contains a Venus Flytrap domain C. Class C – functions as dimers with extracellular glutamate-binding domains D. Class F – all couple to Gαs exclusively

Answer 26

✅ Answer: C. Class C – functions as dimers with extracellular glutamate-binding domains

Question 27

Q5. Which receptor is an example of a Class B GPCR? A. β2-adrenergic receptor B. μ-opioid receptor C. 5HT1A serotonin receptor D. Glucagon-like peptide 1 receptor (GLP-1R)

Answer 27

✅ Answer: D. Glucagon-like peptide 1 receptor (GLP-1R)

Question 28

Q6. Which class of GPCR has the highest number of members in the human genome? A. Class A B. Class B C. Class C D. Class F

Answer 28

✅ Answer: A. Class A

Question 29

Q7. What conformational change in the β2AR is associated with G protein activation? A. Inward shift of TM1 B. Outward movement of TM6 C. Cleavage of the C-terminal domain D. Shortening of intracellular loop 2

Answer 29

✅ Answer: B. Outward movement of TM6

Question 30

Q8. What structural element was used to stabilize β2AR for crystallography at 2.4 Å resolution? A. GFP tag B. Fab5 antibody C. T4 lysozyme fusion in IL3 D. Cholesterol analog

Answer 30

✅ Answer: C. T4 lysozyme fusion in IL3

Question 31

Q9. Which feature of the β2AR’s active site helps initiate the activation process upon agonist binding? A. Transmembrane helix scission B. Rearrangement of side chains in the ligand-binding pocket C. Oligomerization of receptor units D. GTP hydrolysis

Answer 31

✅ Answer: B. Rearrangement of side chains in the ligand-binding pocket

Question 32

Q10. In the active β2AR-Gs protein complex, which G protein subunit directly interacts with the receptor's TM5-TM6 region and ICL2? A. Gαs B. Gβ C. Gγ D. Gαq

Answer 32

✅ Answer: A. Gαs

Question 33

Q11. What experimental strategy was used to prevent the β2AR-Gs complex from dissociating during crystallization? A. Use of cholesterol to anchor the complex B. Cross-linking and nanobody stabilization C. Reconstitution in artificial vesicles D. Mutation of Gα to prevent GTP binding

Answer 33

✅ Answer: B. Cross-linking and nanobody stabilization

Question 34

Q12. What is the role of the α-helical domain of Gαs in GPCR signalling? A. It binds to the ligand directly B. It activates β-arrestin C. It flips to stabilize the nucleotide-free state D. It interacts with the β2AR extracellular loop

Answer 34

✅ Answer: C. It flips to stabilize the nucleotide-free state