G proteins — Identify the false statement about heterotrimeric G protein function and activation state

Difficulty: Easy

Correct Answer: They become activated when bound to GDP

Explanation:


Introduction:
Heterotrimeric G proteins (Gαβγ) couple many cell surface receptors to intracellular effectors. This question asks you to spot the incorrect statement regarding their activation state and role in signaling.


Given Data / Assumptions:

  • G proteins cycle between GDP bound (inactive) and GTP bound (active) forms.
  • G protein coupled receptors act as guanine nucleotide exchange factors upon agonist binding.
  • Downstream effectors include adenylyl cyclase, phospholipase C, and ion channels.


Concept / Approach:
Activation requires exchange of GDP for GTP on Gα. The GTP bound Gα (and Gβγ) then regulate effectors to propagate signals, such as stimulating or inhibiting cAMP synthesis via adenylyl cyclase.


Step-by-Step Solution:

1) Confirm roles: G proteins mediate signal cascades from GPCRs.2) Confirm nucleotide regulation: binding and hydrolysis of guanine nucleotides control activity.3) Identify the false claim: activation with GDP is wrong; GDP corresponds to the inactive state.4) Recognize that active Gα can stimulate or inhibit adenylyl cyclase to modulate cAMP levels.


Verification / Alternative check:
Classical reconstitution studies show GTPγS locks Gα in an active state, continuously stimulating effectors, demonstrating GTP dependence of activation.


Why Other Options Are Wrong (or correct as phrased):

  • Involved in cascades: correct.
  • Bind guanine nucleotides: correct.
  • Active before cAMP production: GPCR–G protein signaling is needed for many cAMP responses.
  • GTP binding to Gα drives effector regulation: correct.


Common Pitfalls:
Mixing up GDP and GTP states. Remember: GDP = off, GTP = on.


Final Answer:
They become activated when bound to GDP.

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