Question

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.

Hint:

GPCRs activate G proteins by exchanging GDP for GTP on the α subunit, which then dissociates from the βγ subunits to activate downstream signaling pathways.

Answer 1

The Correct Option is A, B

To determine which of the given statements about G protein–coupled receptor (GPCR) mediated signaling are correct, let us analyze each option based on established biological principles:

1. GPCRs contain seven membrane spanning regions.
   This statement is correct. G protein-coupled receptors are characterized by their structural feature of having seven transmembrane alpha-helices. These span the cell membrane and are integral to the receptor's ability to transmit signals from outside the cell to the cell's interior.
2. GPCRs are linked to heterotrimeric G protein consisting of α, β and γ subunits.
   This statement is also correct. GPCRs interact with a heterotrimeric G protein composed of three subunits: α (alpha), β (beta), and γ (gamma). Upon activation by a ligand, the GPCR acts as a guanine nucleotide exchange factor, facilitating the exchange of GDP for GTP on the Gα subunit.
3. In the absence of GPCR interacting ligand, α subunit of G protein is bound to GTP and complexed with βγ subunits.
   This statement is incorrect. In the absence of a GPCR interacting ligand, the α subunit of the G protein is actually bound to GDP, not GTP. The α subunit, in the GDP-bound state, is complexed with the βγ dimers. This is the inactive form of the G protein.
4. 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.
   This statement is incorrect. When a ligand binds to the GPCR, GTP, not GDP, displaces GDP on the α subunit. The GTP-bound α subunit then dissociates from the βγ dimer, which allows both the α and the βγ subunits to activate various downstream effectors in the cell, which is the essence of G protein signaling.

Based on the analysis above, the correct statements regarding GPCR-mediated signaling are:

• GPCRs contain seven membrane spanning regions.
• GPCRs are linked to heterotrimeric G protein consisting of α, β and γ subunits.