G protein-Coupled Receptors: Videos & Practice Problems

G protein-coupled receptors (GPCRs) are integral membrane proteins characterized by seven transmembrane alpha helices. Upon ligand binding, GPCRs undergo a conformational change, activating associated G proteins, which can be stimulatory (G_s) or inhibitory (G_i). G proteins consist of three subunits: alpha, beta, and gamma. The activated alpha subunit interacts with effector enzymes to produce secondary messengers, crucial for signal transduction pathways that lead to cellular responses. Understanding these components is essential for grasping cellular communication mechanisms.

G protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are integral membrane proteins that play a crucial role in cellular signaling. They are characterized by their structure, which consists of seven transmembrane alpha helices, often referred to as 7 TMS proteins. These helices span the cell membrane and are essential for the receptor's function. Each GPCR has an extracellular N-terminal domain and an intracellular C-terminal domain, which are vital for their interaction with other cellular components.

In their active state, GPCRs couple with G proteins, which are intracellular proteins that bind guanosine triphosphate (GTP). G proteins are known as heterotrimeric because they consist of three different subunits: alpha, beta, and gamma. The alpha subunit is particularly important as it is responsible for the GTP hydrolysis process, converting GTP to guanosine diphosphate (GDP) and releasing energy. This hydrolysis is crucial for the activation and deactivation of signaling pathways within the cell.

GTP and ATP are both high-energy molecules, but they differ in their nitrogenous bases. While ATP is well-known for its role in energy transfer, GTP serves a similar function in signaling pathways. The hydrolysis of GTP to GDP signifies a transition from an active to an inactive state for the G protein, analogous to the conversion of ATP to ADP.

Understanding the structure and function of GPCRs and their associated G proteins is fundamental in cell biology, as they are involved in various physiological processes and are targets for many therapeutic drugs. As we delve deeper into the mechanisms of GPCR signaling, the importance of these receptors in health and disease will become increasingly evident.

G protein-Coupled Receptors

G protein-coupled receptors (GPCRs) play a crucial role in cellular communication and signal transduction. Understanding the fundamental components of GPCR signal transduction pathways is essential for grasping how cells respond to external signals. The three primary components involved in these pathways are the GPCR itself, the G protein, and the effector enzyme.

The GPCR is a transmembrane receptor that undergoes a conformational change upon ligand binding. This change is vital as it activates the associated G protein. When a ligand binds to the GPCR, it triggers this conformational shift, allowing the G protein to become activated. The G protein is an intracellular lipid-linked peripheral membrane protein that can bind to guanosine diphosphate (GDP) and guanosine triphosphate (GTP). Upon activation, GDP is replaced by GTP, transitioning the G protein from its inactive state to an active one. The G protein consists of three subunits: alpha, beta, and gamma. When activated, the G protein dissociates into the GTP-bound alpha subunit and the beta-gamma complex.

The third component, the effector enzyme, is a membrane-bound protein that is activated by the GTP-bound alpha subunit. The primary function of the effector enzyme is to produce secondary messengers, which are crucial for propagating the signal within the cell. These secondary messengers can vary depending on the specific GPCR pathway but are essential for eliciting a cellular response. The overall process can be summarized as follows: a ligand binds to the GPCR, causing a conformational change that activates the G protein, leading to the dissociation of the alpha subunit. This active alpha subunit then activates the effector enzyme, which generates secondary messengers that ultimately result in a cellular response.

In summary, the GPCR, G protein, and effector enzyme are integral components of GPCR signal transduction pathways. Their interactions facilitate the conversion of an extracellular signal into a specific cellular response, highlighting the complexity and efficiency of cellular communication mechanisms.

A G protein-coupled receptor is comprised of ____ transmembrane α-helix/helices:

• A. 7.
• B. 8.
• C. 1.
• D. 10.
• E. 6.
• F. 14.

Answer: (A)

G protein-coupled receptors (GPCRs) are transmembrane proteins with ligand binding sites on the extracellular side of the membrane (near its N-terminal). What is the role of the G-protein in the GPCR signaling pathway?

• A. G proteins phosphorylate GPCRs.
• B. G proteins bind extracellular ligands and facilitate the transport into the cell.
• C. G proteins activate enzymes that transduce the signal throughout the cell.
• D. G proteins activate transcription of genes.
• E. G proteins facilitate dimerization of receptor monomers.

Answer: (C)

G protein-Coupled Receptors

G proteins play a crucial role in cellular signaling by interacting with effector enzymes, which can either be activated or inhibited depending on the type of G protein involved. There are two primary classifications of G proteins based on their effects: stimulatory G proteins (Gs) and inhibitory G proteins (Gi).

The stimulatory G protein, known as Gs, functions to activate the effector enzyme, leading to an increased production of secondary messengers. This can be likened to pressing the gas pedal in a car, which accelerates its speed. When Gs is activated, it binds to GTP and dissociates, allowing it to stimulate the effector enzyme effectively.

In contrast, the inhibitory G protein, abbreviated as Gi, serves to inhibit the effector enzyme, resulting in a decreased production of secondary messengers. This is analogous to applying the brakes in a car, which slows down its speed. Similar to Gs, Gi also binds to GTP; however, its role is to inhibit the activity of the effector enzyme.

Understanding the distinction between these two types of G proteins is essential for grasping how cellular signaling pathways are regulated. As we progress in our studies, we will explore specific examples of both stimulatory and inhibitory G proteins, deepening our comprehension of their functions and implications in various biological processes.

G_i is the inhibitory G protein of various effector enzymes. If a toxin released from a bacterial infection enters cells & covalently modifies the α-subunit of G_i so that it can no longer bind GTP, which of the following is a likely result?

• A. Increase in the synthesis of the secondary messenger molecule.
• B. Decrease in the synthesis of the secondary messenger molecule.
• C. The inhibitory G protein α-subunit will not dissociate from the β-γ subunits.
• D. Only A and C are true.
• E. Only B and C are true.

Answer: (D)

Here’s what students ask on this topic:

What are G protein-coupled receptors (GPCRs) and their main structural features?

G protein-coupled receptors (GPCRs) are integral membrane proteins characterized by seven transmembrane alpha helices. These receptors are also known as 7 TMS proteins due to their seven transmembrane segments. GPCRs have an extracellular N-terminal and an intracellular C-terminal. Upon ligand binding, GPCRs undergo a conformational change, which activates associated G proteins. These G proteins are intracellular lipid-linked proteins that can bind and hydrolyze GTP. The activation of G proteins leads to various cellular responses through signal transduction pathways.

How do G proteins associated with GPCRs function?

G proteins associated with GPCRs function by binding and hydrolyzing GTP. They consist of three subunits: alpha, beta, and gamma. Upon activation by a GPCR, the G protein exchanges GDP for GTP, causing the alpha subunit to dissociate from the beta and gamma subunits. The activated alpha subunit then interacts with effector enzymes to produce secondary messengers, which propagate the signal within the cell. This process is crucial for various cellular responses and signal transduction pathways.

What are the three essential components of GPCR signal transduction pathways?

The three essential components of GPCR signal transduction pathways are: 1) the GPCR itself, which undergoes a conformational change upon ligand binding; 2) the G protein, which binds and hydrolyzes GTP, and consists of alpha, beta, and gamma subunits; and 3) the effector enzyme, a membrane-bound enzyme activated by the G protein's alpha subunit. The effector enzyme produces secondary messengers that affect downstream targets, leading to the cell's response.

What is the difference between stimulatory and inhibitory G proteins?

Stimulatory G proteins (Gs) and inhibitory G proteins (Gi) differ in their effects on effector enzymes. Stimulatory G proteins activate effector enzymes, increasing the production of secondary messengers, similar to pressing a gas pedal in a car. In contrast, inhibitory G proteins inhibit effector enzymes, reducing the production of secondary messengers, akin to applying brakes in a car. Both types of G proteins play crucial roles in regulating cellular responses through GPCR signal transduction pathways.

What role do secondary messengers play in GPCR signal transduction pathways?

Secondary messengers play a crucial role in GPCR signal transduction pathways by propagating the signal initiated by the ligand binding to the GPCR. Once the GPCR activates the G protein, the G protein's alpha subunit activates an effector enzyme, which then produces secondary messengers. These secondary messengers, such as cAMP or IP3, amplify the signal and activate downstream targets within the cell, ultimately leading to a specific cellular response. This process ensures that the initial extracellular signal is effectively transmitted and amplified within the cell.