Q.33 Which of the following statements is/are CORRECT for G protein–coupled receptor (GPCR)
mediated signaling?
(A) GPCRs contain seven membrane spanning regions.
(B) GPCRs are linked to heterotrimeric G protein consisting of α, β and γ subunits.
(C) In the absence of GPCR interacting ligand, α subunit of G protein is bound to GTP and
complexed with βγ subunits.
(D) In the presence of GPCR interacting ligand, GTP is displaced from α subunit of G protein
by GDP, GDP bound α subunit dissociates from βγ dimer and activates the effector.

G Protein-Coupled Receptor (GPCR) Signaling: CSIR NET MCQ Solved with Detailed Analysis

G Protein-Coupled Receptors (GPCRs) mediate vital cellular signaling through interaction with heterotrimeric G proteins. Options (A) and (B) are correct, while (C) and (D) contain errors in nucleotide binding and activation sequence.

Option Analysis

GPCRs represent the largest receptor family, crucial for CSIR NET cell signaling topics.

• (A) Correct: GPCRs feature seven α-helical transmembrane domains (7-TM), connected by extracellular and intracellular loops, forming their signature serpentine structure.

• (B) Correct: GPCRs couple to heterotrimeric G proteins (Gα, Gβ, Gγ subunits); Gα binds nucleotides, while Gβγ modulates effectors.

• (C) Incorrect: In the ligand-free state, inactive Gα binds GDP (not GTP) and remains complexed with Gβγ; GTP binding activates dissociation.

• (D) Incorrect: Ligand binding induces GDP release from Gα (not GTP displacement), allowing GTP binding; GTP-Gα then dissociates from Gβγ to activate effectors like adenylyl cyclase.

Activation Mechanism

Ligand binding to GPCR extracellular domain triggers conformational change, exposing intracellular loops that act as GEF for Gα.

GPCR signaling cycle:

• Inactive: GDP-Gαβγ trimer associates with GPCR.

• Activation: Ligand-bound GPCR catalyzes GDP → GTP exchange on Gα.

• Dissociation: GTP-Gα and Gβγ separately activate effectors (e.g., Gsα stimulates cAMP production).

• Termination: Intrinsic GTPase of Gα hydrolyzes GTP → GDP, reforming trimer.