33. G protein-coupled receptors (GPCRs) are used to detect and respond to many different types of signals, including neurotransmitters, hormones involved in glycogen and fat metabolism and even photons of light. Which one of the following statements regarding GPCR is INCORRECT?
(1) GPCRs are a large family with a common structure of seven membrane spanning a helices.
(2) GPCRs are coupled to trimeric G proteins comprising three subunits α, β and γ
(3) The G_α subunit is a GTPase switch protein that alternates between an active (‘on’) state with bound GTP and an inactive (‘off’) state with GDP.
(4) The ‘on’ form gets bound to β and γ subunits and activates a membrane bound effector like adenylyl cyclase. Phospholipase C or ion channel.

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Introduction

G-protein coupled receptors (GPCRs) represent a vast and diverse family of membrane proteins critical to cellular responses to hormones, neurotransmitters, and sensory signals. They share a characteristic structure and a well-established mechanism of activating intracellular G proteins to transmit signals.

Key Correct Features of GPCRs

1. Seven Transmembrane Helices: GPCRs have a shared structural motif consisting of seven membrane-spanning alpha helices that create a ligand-binding pocket within the membrane.

2. Trimeric G Protein Coupling: These receptors interact with heterotrimeric G proteins composed of alpha (α), beta (β), and gamma (γ) subunits.

3. Gα Subunit Function: The Gα subunit acts as a molecular switch with intrinsic GTPase activity, cycling between active (GTP-bound) and inactive (GDP-bound) states.

The Common False Statement Explained

The incorrect statement is:

“The ‘on’ form gets bound to β and γ subunits and activates a membrane bound effector like adenylyl cyclase, phospholipase C or ion channel.”

This is false because when the Gα subunit is in the active GTP-bound state, it dissociates from the βγ dimer. The free Gα subunit and the free βγ dimer can both independently modulate downstream effectors. Thus, the active Gα subunit is not bound to the β and γ subunits while activating effectors.

Summary Table

References

This clarification aligns with crystal structures and biochemical data from sources including nature reviews, NCBI articles, and thorough reviews of GPCR structural biology.

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