G Protein Coupled Receptors(GPCRs) - Structure, Function, Mechanism of Action. Everything!

Summary

This video delves into G-protein coupled receptors (GPCRs), highlighting their structure, function, and mechanism of action. GPCRs are transmembrane proteins that span the plasma membrane seven times, with an extracellular and intracellular domain. Ligands bind to the extracellular domain, triggering intracellular signaling. G proteins, consisting of alpha, beta, and gamma subunits, interact with activated GPCRs to relay signals and elicit cellular effects. The video also explores two key pathways: adenylyl cyclase, which converts ATP to cyclic AMP, and phospholipase C, which cleaves phosphatidylinositol bisphosphate into diacylglycerol and inositol triphosphate, leading to increased cytosolic calcium ion concentration and activation of certain enzymes.

Takeaways

• 🧬 G-protein coupled receptors (GPCRs) are transmembrane proteins that span the plasma membrane seven times.
• 🔗 GPCRs have an N-terminal extracellular domain for ligand binding and a C-terminal intracellular domain for signal transduction.
• 🔑 Ligands, such as peptide hormones, bind to the extracellular domain of GPCRs to initiate signaling.
• 🌐 G proteins are composed of three subunits: alpha, beta, and gamma, with the gamma subunit anchored to the membrane.
• ⏱️ Upon agonist binding, GPCRs undergo a conformational change that activates associated G proteins within about 50 milliseconds.
• 🔄 The activation of G proteins involves the exchange of GDP for GTP, leading to the separation of alpha and beta-gamma subunits.
• 🔋 Alpha GTP and beta-gamma dimers are the active forms of G proteins that interact with effector enzymes and ion channels.
• 📈 There are four types of G proteins with pharmacological importance: Gs, Gi, Gq, and Gn proteins.
• 🔄 The adenylyl cyclase pathway involves the conversion of ATP to cyclic AMP (cAMP), which activates protein kinases.
• 🌀 The phospholipase C pathway involves the cleavage of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3).
• 📈 IP3 increases cytosolic calcium ion concentration, which aids in muscle contraction and enzyme activation, while DAG activates protein kinase C (PKC).

Q & A

What are G-protein coupled receptors (GPCRs)?

GPCRs are transmembrane proteins made up of a single polypeptide chain that spans the plasma membrane seven times. They play a crucial role in signal transduction by binding extracellular signaling molecules and initiating intracellular responses.

How do ligands interact with GPCRs?

Ligands, such as peptide hormones, bind to the extracellular domain of GPCRs. This binding cannot pass through the cell membrane and triggers intracellular signaling cascades that mediate the functions of the specific ligand.

What is the structure of G proteins?

G proteins are a group of membrane-bound proteins consisting of three subunits: alpha, beta, and gamma. The gamma subunit is anchored to the plasma membrane via a fatty acid chain.

What happens when an agonist binds to a GPCR?

Upon agonist binding, a conformational change occurs in the receptor, which interacts with the G protein. This interaction leads to the dissociation of GDP from the alpha subunit and the binding of GTP, activating the G protein.

What are the active forms of G proteins after activation?

The active forms of G proteins are the alpha GTP fragment and the beta gamma dimer. These components can interact with effector enzymes and other cellular targets to elicit cellular responses.

What are the four types of pharmacologically important G proteins?

The four types of pharmacologically important G proteins are Gs (stimulatory), Gi (inhibitory), Gq, and G12/13 proteins. Each type plays a distinct role in cellular signaling.

How does the adenylyl cyclase pathway work?

In the adenylyl cyclase pathway, the enzyme adenylyl cyclase is activated by Gs proteins and inhibited by Gi proteins. When activated, it converts ATP into cyclic AMP, which in turn activates protein kinases that cause the phosphorylation of certain enzymes.

What is the role of phospholipase C in GPCR signaling?

In the phospholipase C pathway, the agonist-bound receptor activates a Gq protein, which then activates phospholipase C. This enzyme cleaves phosphatidylinositol bisphosphate into diacylglycerol and inositol triphosphate (IP3), leading to calcium ion release and activation of protein kinase C.

What is the function of IP3 in the cell?

IP3 binds to its receptor on the endoplasmic reticulum, causing the release of calcium ions into the cytoplasm. This increase in cytosolic calcium ion concentration aids in muscle contraction and the activation of certain enzymes.

How does diacylglycerol (DAG) contribute to cellular signaling?

DAG causes an increase in protein kinase C (PKC) levels within the cell. Activated PKC can then phosphorylate certain enzymes and proteins, leading to various cellular responses.