G Protein-Coupled Receptors (GPCR) Lecture Flashcards

Vocabulary terms and definitions covering G Protein-Coupled Receptor (GPCR) structure, signalling cycles, G protein subtypes, and termination mechanisms.

G Protein-Coupled Receptors (GPCR)

A major class of mammalian receptors, often called 7 transmembrane receptors or metabotropic receptors, with approximately 800 types in humans that lack intrinsic enzymic activity.

Heterotrimeric G-protein

A protein complex consisting of three subunits ($\alpha$, $\beta$, and $\gamma$) that controls the activity of an effector protein such as an enzyme or ion channel.

Effector Protein

A protein, such as an enzyme or ion channel, whose activity is regulated by G-proteins to produce second messengers or change membrane potential.

Second Messengers

Molecules like $\text{cAMP}$, $Ca^{2+}$, or $IP_3$ that are generated following GPCR activation to relay signals to target proteins.

G Protein Activation State

The protein is inactive when bound to $\text{GDP}$ and becomes active when bound to $\text{GTP}$.

GTPase activity

An intrinsic property of G proteins that converts bound $\text{GTP}$ to $\text{GDP}$, effectively turning the G protein off.

GEF (Guanine nucleotide exchange factor)

A factor that stimulates the displacement of $\text{GDP}$ by $\text{GTP}$ to activate G proteins; activated GPCRs can act as GEFs.

GAP (GTPase activating proteins)

Also called Regulators of G-Protein Signalling (RGS), these proteins enhance G-protein inactivation by activating GTPase activity.

Conformational change in GPCR activation

Upon ligand binding, the transmembrane helix $TM5$ extends and $TM6$ is displaced to open a binding interface for the G protein.

$$G\alpha_s$$

A G protein subtype that activates adenylyl cyclase to stimulate the production of $\text{cAMP}$.

$$G\alpha_i$$

A G protein subtype that inhibits adenylyl cyclase activity.

$$G\alpha_q$$

A G protein subtype that activates phospholipase $C\beta$, leading to $IP_3$/$DAG$ signalling.

$$G\alpha_{12/13}$$

A G protein subtype primarily involved in regulating Rho signalling.

Cholera Toxin

A toxin that inhibits $G\alpha_s$ GTPase activity, leading to persistent stimulation of adenylyl cyclase.

Pertussis Toxin

A toxin that acts by inhibiting the $G\alpha_i$ subunit.

GIRK channel

G protein-coupled inwardly-rectifying potassium channel that is opened by the binding of $G\beta\gamma$ subunits, leading to membrane hyperpolarization.

Desensitization

A process to terminate GPCR signalling involving phosphorylation by GRK and the subsequent binding of $\beta$-arrestin.

GRK (G protein-coupled receptor kinase)

An enzyme that phosphorylates activated GPCRs to initiate the desensitization process.

$\beta$-arrestin

A protein that binds to phosphorylated GPCRs to block further G-protein coupling and facilitate receptor internalization via clathrin-coated pits.

Ligand-Gated Ion Channels

Also known as ionotropic receptors, these include nicotinic ACh receptors and $GABA_A$ receptors, which change from a closed ($0.3\,nm$) to an open ($0.7\,nm$) state upon ligand binding.