G Protein Coupled Receptors | Nervous system physiology | NCLEX-RN | Khan Academy

Summary

This video delves into G-protein coupled receptors (GPCRs), the largest class of membrane receptors found in eukaryotes. Humans possess over 1,000 types of GPCRs, each with a specific function, and they are targeted by 30-50% of modern drugs. GPCRs, characterized by seven transmembrane alpha helices, interact with G-proteins to regulate a myriad of cellular functions, including immune response, growth, and mood. The video explains the structural uniqueness of GPCRs, their interaction with G-proteins, and the signaling pathway involving ligand binding, conformational changes, and the production of second messengers like cyclic AMP, which influences various bodily functions.

Takeaways

• 🔬 G-protein coupled receptors (GPCRs) are the largest class of membrane receptors found only in eukaryotes, with humans having over 1,000 types.
• 💊 GPCRs are crucial in pharmacology, as they are the target for 30-50% of modern medicinal drugs.
• 🔄 They interact with a wide array of ligands, including light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters.
• 🌟 GPCRs play a significant role in regulating immune system, growth, smell, taste, vision, behavior, and mood, including serotonin and dopamine.
• 🏅 The importance of GPCRs is underscored by the 2012 Nobel Prize in Chemistry awarded for their research.
• 🧬 GPCRs are characterized by having seven transmembrane alpha helices, earning them the nickname '7 transmembrane receptors'.
• 🔗 GPCRs are coupled with G-proteins, which are heterotrimeric proteins consisting of alpha, beta, and gamma subunits.
• ⚙️ Activation of GPCRs by ligands triggers a conformational change, leading to the exchange of GDP for GTP in the alpha subunit and subsequent dissociation from beta and gamma subunits.
• 📡 The alpha subunit and beta-gamma dimer can regulate target proteins, such as enzymes or ion channels, initiating a cascade of cellular responses.
• 🔙 The cycle resets when GTP is hydrolyzed back to GDP, a process that can be accelerated by RGS proteins for precise regulation.
• 🌡️ An example of GPCR function is the response to epinephrine, which leads to increased heart rate and dilated blood vessels as part of the fight or flight response.

Q & A

What are G-protein coupled receptors (GPCRs)?

GPCRs are a large class of membrane receptors found only in eukaryotes, with humans having over 1,000 different types. They are unique due to their seven transmembrane alpha helices and are involved in a wide range of functions, including immune system regulation, growth, and mood.

Why are GPCRs significant in medicinal drugs?

GPCRs are the target of around 30 to 50% of all modern medicinal drugs due to their role in regulating various physiological processes. Their ability to bind to a wide variety of ligands makes them a key point of intervention for many therapeutic strategies.

What types of ligands can bind to GPCRs?

GPCRs can bind to a diverse range of ligands, including light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters such as serotonin and dopamine.

What is the structural characteristic that defines GPCRs?

GPCRs are characterized by having seven transmembrane alpha helices, which is why they are also known as '7 transmembrane receptors'. This structure allows them to span the cell membrane seven times.

How are GPCRs associated with G-proteins?

GPCRs interact with G-proteins, which are specialized proteins capable of binding GTP and GDP. The G-proteins associated with GPCRs are heterotrimeric, consisting of alpha, beta, and gamma subunits.

What happens when a ligand binds to a GPCR?

Upon ligand binding, GPCRs undergo a conformational change. This change triggers a series of events, including the exchange of GDP for GTP in the alpha subunit of the associated G-protein, leading to the dissociation of the alpha subunit from the beta and gamma subunits.

What is the role of the alpha subunit after GTP binding?

Once the alpha subunit binds GTP, it dissociates from the beta and gamma subunits and can regulate the function of other proteins in the cell, such as enzymes or ion channels, which can act as second messengers.

How does the signal continue after the alpha subunit interacts with a target protein?

After the alpha subunit activates a target protein, it can relay a signal. This signal can be amplified through the production of second messengers, which then initiate a cascade of cellular responses.

What is the purpose of the GTP hydrolysis step in the GPCR signaling pathway?

The hydrolysis of GTP to GDP is a critical step that allows the G-protein to return to its inactive state, terminating the signal. This process can be regulated by proteins like RGS, which can accelerate the hydrolysis.

Can you provide an example of GPCR function in the body?

A common example is the binding of epinephrine (adrenaline) to adrenergic receptors, which triggers a conformational change, leading to the activation of adenylate cyclase and the production of cyclic AMP. This second messenger can then increase heart rate, dilate blood vessels, and stimulate glycogen breakdown into glucose.

How do GPCRs regulate a range of bodily functions?

GPCRs regulate bodily functions by responding to external signals through a series of events that include G-protein activation and the production of second messengers. This complex signaling pathway can influence functions from sensation to growth and hormone response.