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Questions and Answers
What is the primary function of metabotropic receptors?
What is the primary function of metabotropic receptors?
How many transmembrane α-helices do G-protein coupled receptors (GPCRs) typically possess?
How many transmembrane α-helices do G-protein coupled receptors (GPCRs) typically possess?
What is the role of the third intracellular loop (i3) in GPCRs?
What is the role of the third intracellular loop (i3) in GPCRs?
What is a key feature of the structure of metabotropic receptors?
What is a key feature of the structure of metabotropic receptors?
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Why is knowledge of cell signalling crucial in biochemistry?
Why is knowledge of cell signalling crucial in biochemistry?
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What type of receptors do G-proteins couple to?
What type of receptors do G-proteins couple to?
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What modification near the N-terminus of GPCRs is important for membrane trafficking?
What modification near the N-terminus of GPCRs is important for membrane trafficking?
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What is the significance of the 865 currently known GPCRs?
What is the significance of the 865 currently known GPCRs?
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What effect does disruption of disulphide bonds have on ligand binding?
What effect does disruption of disulphide bonds have on ligand binding?
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Replacing cysteine in the C-terminal domain affects which aspect of receptor function?
Replacing cysteine in the C-terminal domain affects which aspect of receptor function?
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Which G-proteins are thought to activate processes linked to different effector molecules?
Which G-proteins are thought to activate processes linked to different effector molecules?
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What initiates the signalling cascade in the fight or flight response?
What initiates the signalling cascade in the fight or flight response?
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What is the main consequence of the cholera toxin's action on G-protein signaling?
What is the main consequence of the cholera toxin's action on G-protein signaling?
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Excess chloride transport into the lumen due to cholera toxin leads to what physiological effect?
Excess chloride transport into the lumen due to cholera toxin leads to what physiological effect?
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Which pathway is primarily activated by the binding of adrenaline to its receptor?
Which pathway is primarily activated by the binding of adrenaline to its receptor?
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What type of protein is produced by the cholera-causing organism Vibrio cholera?
What type of protein is produced by the cholera-causing organism Vibrio cholera?
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Study Notes
Metabotropic Receptors
- Metabotropic receptors are slower but have a longer-lasting effect than ionotropic receptors.
- They utilize a series of metabolic processes, often involving enzyme activation, to transduce signals.
- An example of this process is the fight-or-flight response.
Learning Outcomes
- Explain the principles of cell signaling and signal transduction.
- Define metabotropic receptors and G-protein-coupled receptors.
- Explain the structure of G-protein-coupled receptors and how this impacts their activity.
- Explain the actions of a G-protein when a ligand binds.
- Explain GPCR signaling transduction.
Cell Signaling and Signal Transduction
- Cell signaling is a crucial aspect of modern biochemistry and cell biology.
- It's essential for cell-cell communication and coordinated cellular function in all organisms.
- Understanding cell signaling is crucial for comprehending various diseases, like cancer and diabetes.
Types of Receptors
- Receptors can be broadly categorized into ligand-gated ion channels, G-protein-coupled receptors, kinase-linked receptors, and nuclear receptors.
- Each type of receptor mediates signals differently, impacting cellular responses in various ways.
- Receptors have diverse time scales for their effects, ranging from milliseconds to hours.
Receptor Names
- Metabotropic receptors mediate their effects by activating a series of metabolic processes, usually involving enzyme activation to transduce the signal.
- 7-transmembrane G-protein-coupled receptors are a specific type and are characterized by their structure and mechanism of transducing chemical signals.
Type 2: G-protein-coupled Receptors
- G protein-coupled receptors (GPCRs) are transmembrane receptors, typically spanning the cell membrane seven times.
- They are composed of 400-500 polypeptide chains.
- GPCRs employ G proteins to mediate their interactions with intracellular effector systems.
- This receptor family is one of the largest and is a common therapeutic target for various drugs.
Structure of GPCRs
- GPCRs have seven transmembrane α-helices that are largely conserved.
- The extracellular N-terminus and intracellular C-terminus exhibit variation in length and sequence.
- The third intracellular loop is highly variable.
Modifications to GPCR Structure
- Glycosylation, with carbohydrates bonded near the N-terminus, plays a critical role in membrane traffic and insertion, but not in ligand binding.
Ligand Binding Capacity
- Disulfide bonds connect cysteines in loops E2 and E3.
- Disruption of these bonds can reduce ligand binding capacity.
Effectiveness of Cellular Response
- Cysteine residues in the C-terminal domain stabilize receptor-membrane interactions.
- Replacing these cysteines doesn't affect ligand binding but may reduce G-protein coupling.
Protein Coupling
- Different G protein subtypes exist.
- The α-subunit largely determines the subtype (e.g., G₂, G₁, Gq, or G₁₃).
Type 2: G protein-coupled Receptors
- Different G proteins activate different effector molecules, like enzymes and ion channels.
- Examples include adenylyl cyclase and phospholipase C.
- Alpha subunits define the subtypes (Gs, G₁, Gq, or G₁₃).
Signaling Pathway Involving Second Messengers IP₃ and Ca²⁺
- Signaling pathways trigger responses like changes in cell metabolism, activation of gene activity, or opening or closure of ion channels.
- Second messengers like IP₃ and Ca²⁺ are involved in these processes.
Fight-or-Flight Pathway
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Adrenaline, a hormone released by the adrenal gland, plays a key role in the fight-or-flight response.
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It travels through the bloodstream to muscle and liver cells and binds to G protein-coupled receptors.
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The binding triggers a cascade of events that result in glucose release to prepare the body for action.
Disease Associated with G-proteins (Cholera)
- Vibrio cholera toxin affects intestinal epithelial cells.
- Beta subunits of the toxin attach to the cells, and alpha subunits activate adenylyl cyclase.
- High cAMP levels lead to chloride transport into the lumen and sodium absorption.
- These processes result in water loss.
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Description
This quiz explores the principles of cell signaling and the role of metabotropic receptors in signal transduction. You'll learn about G-protein-coupled receptors, their structure, and their impact on cellular functions. Understanding these concepts is vital for grasping their implications in various diseases.
