Podcast
Questions and Answers
What is the significance of the fact that GPCRs constitute the single largest protein superfamily encoded by animal genomes?
What is the significance of the fact that GPCRs constitute the single largest protein superfamily encoded by animal genomes?
- It indicates that GPCRs have evolved to be highly efficient in their function.
- It demonstrates the importance of GPCRs in drug discovery. (correct)
- It implies that GPCRs are particularly susceptible to mutations.
- It suggests that GPCRs are essential for a wide range of cellular processes. (correct)
Why are G protein-coupled receptors (GPCRs) also referred to as seven-transmembrane receptors?
Why are G protein-coupled receptors (GPCRs) also referred to as seven-transmembrane receptors?
- They are activated by seven distinct signaling pathways.
- They have seven transmembrane domains that span the cell membrane. (correct)
- They interact with seven different G proteins.
- They are involved in seven major cellular processes.
What is the implication of the finding that inactivating mutations in GPCRs are linked to over 30 human diseases?
What is the implication of the finding that inactivating mutations in GPCRs are linked to over 30 human diseases?
- GPCRs play a critical role in maintaining human health. (correct)
- Mutations in GPCRs are a common cause of disease.
- GPCRs are highly susceptible to mutations.
- GPCRs are the primary targets for drug development.
Which of the following is NOT an example of a natural ligand that binds to GPCRs?
Which of the following is NOT an example of a natural ligand that binds to GPCRs?
What is the function of olfactory sensory neurons in vertebrates?
What is the function of olfactory sensory neurons in vertebrates?
What is the significance of the similarity between the odorant-binding pocket in OR51E2 and the binding pockets of other class A GPCRs?
What is the significance of the similarity between the odorant-binding pocket in OR51E2 and the binding pockets of other class A GPCRs?
What is the role of Gαs in the activation of OR51E2?
What is the role of Gαs in the activation of OR51E2?
What is the likely consequence of a mutation in the transmembrane domain of an odorant receptor?
What is the likely consequence of a mutation in the transmembrane domain of an odorant receptor?
What is the function of adenylate cyclase in the context of the provided text?
What is the function of adenylate cyclase in the context of the provided text?
What is the primary function of the transmembrane domain bundle (TM) in the AC9-Gαs complex?
What is the primary function of the transmembrane domain bundle (TM) in the AC9-Gαs complex?
What does the term 'heterotrimeric' refer to in the context of G proteins?
What does the term 'heterotrimeric' refer to in the context of G proteins?
The text mentions a change in conformation in the receptor molecule. What does this change in conformation directly lead to?
The text mentions a change in conformation in the receptor molecule. What does this change in conformation directly lead to?
Which of the following statements accurately describes the role of the α subunit in the G protein?
Which of the following statements accurately describes the role of the α subunit in the G protein?
What is the significance of the lipid chains attached to the α and γ subunits of the G protein?
What is the significance of the lipid chains attached to the α and γ subunits of the G protein?
The activation of a single receptor can lead to the activation of multiple G protein molecules. This phenomenon is referred to as:
The activation of a single receptor can lead to the activation of multiple G protein molecules. This phenomenon is referred to as:
Based on the content, what can be inferred about the role of the AC9-Gαs complex in cellular signaling?
Based on the content, what can be inferred about the role of the AC9-Gαs complex in cellular signaling?
What is the primary function of phospholipids in cell membranes?
What is the primary function of phospholipids in cell membranes?
Which of the following is NOT a lipid-derived second messenger?
Which of the following is NOT a lipid-derived second messenger?
What is a growth factor?
What is a growth factor?
How do growth factors typically act on their target cells?
How do growth factors typically act on their target cells?
What is the significance of the increase in phosphoinositides levels in cells treated with growth factors?
What is the significance of the increase in phosphoinositides levels in cells treated with growth factors?
Which of the following statements about phospholipids is TRUE?
Which of the following statements about phospholipids is TRUE?
What is the most likely outcome of a mutation that prevents the production of a specific growth factor?
What is the most likely outcome of a mutation that prevents the production of a specific growth factor?
Why are growth factors important for cellular development?
Why are growth factors important for cellular development?
What is the role of cyclic AMP (cAMP) in the breakdown of glycogen?
What is the role of cyclic AMP (cAMP) in the breakdown of glycogen?
What is the significance of the 'substance' identified by Sutherland as cyclic AMP?
What is the significance of the 'substance' identified by Sutherland as cyclic AMP?
In the context of the described experiment, why was the hormone-treated particulate fraction washed and the wash added to the supernatant?
In the context of the described experiment, why was the hormone-treated particulate fraction washed and the wash added to the supernatant?
What is the primary function of the protein kinase activated by cAMP, in the context of glycogen breakdown?
What is the primary function of the protein kinase activated by cAMP, in the context of glycogen breakdown?
Which of the following statements accurately describes the role of a second messenger in cell signaling?
Which of the following statements accurately describes the role of a second messenger in cell signaling?
What is the key difference between the hormone and the second messenger (cAMP)?
What is the key difference between the hormone and the second messenger (cAMP)?
How does the activation of phosphorylase lead to glycogen breakdown?
How does the activation of phosphorylase lead to glycogen breakdown?
What is a plausible explanation for the observation that the hormone-treated particulate fraction, when washed and its wash added to the supernatant, activated phosphorylase?
What is a plausible explanation for the observation that the hormone-treated particulate fraction, when washed and its wash added to the supernatant, activated phosphorylase?
What is the specific phosphoinositide that FYVE and PX domains bind to?
What is the specific phosphoinositide that FYVE and PX domains bind to?
What is the role of the PLC isoforms in phospholipid binding?
What is the role of the PLC isoforms in phospholipid binding?
Which of the following domains is NOT involved in phosphoinositide recognition?
Which of the following domains is NOT involved in phosphoinositide recognition?
What is the term used for the family of enzymes that catalyze the phosphorylation of the 3-position of the inositol ring in phosphoinositides?
What is the term used for the family of enzymes that catalyze the phosphorylation of the 3-position of the inositol ring in phosphoinositides?
Which phosphoinositide is specifically recognized by pleckstrin homology (PH) domains?
Which phosphoinositide is specifically recognized by pleckstrin homology (PH) domains?
Which of the following is true about the interaction of FYVE and PX domains with membranes?
Which of the following is true about the interaction of FYVE and PX domains with membranes?
What is the role of enzymes like PTEN and SHIP in PI metabolism?
What is the role of enzymes like PTEN and SHIP in PI metabolism?
What is the primary function of phosphoinositide kinases in PI metabolism?
What is the primary function of phosphoinositide kinases in PI metabolism?
Which of the following enzymes are involved in the dephosphorylation of key tyrosine residues (pY) on cyclin-dependent kinases (cdks)?
Which of the following enzymes are involved in the dephosphorylation of key tyrosine residues (pY) on cyclin-dependent kinases (cdks)?
What is the significance of the CX5R signature in the context of dual-specificity phosphatases (DSPs)?
What is the significance of the CX5R signature in the context of dual-specificity phosphatases (DSPs)?
Which type of phosphatase utilizes Asp-based catalysis?
Which type of phosphatase utilizes Asp-based catalysis?
What is the role of FCP/SCP in the regulation of RNA polymerase II?
What is the role of FCP/SCP in the regulation of RNA polymerase II?
What is the primary role of the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II?
What is the primary role of the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II?
What is the primary function of LMWPTPs?
What is the primary function of LMWPTPs?
Which of the following statements is TRUE about the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II?
Which of the following statements is TRUE about the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II?
Why are dual-specificity phosphatases (DSPs) known as a diverse bunch?
Why are dual-specificity phosphatases (DSPs) known as a diverse bunch?
Flashcards
G Protein-Coupled Receptors (GPCRs)
G Protein-Coupled Receptors (GPCRs)
Membrane proteins that interact with G proteins and have 7 transmembrane helices.
Natural ligands
Natural ligands
Molecules like hormones and neurotransmitters that bind to GPCRs to activate them.
Olfactory Receptors (ORs)
Olfactory Receptors (ORs)
A subtype of GPCRs that detect odorants in the sensory neurons.
C.elegans GPCRs
C.elegans GPCRs
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GPCR drug target
GPCR drug target
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Inactivating mutations
Inactivating mutations
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Transmembrane helices
Transmembrane helices
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cAMP in GPCR signaling
cAMP in GPCR signaling
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Crude extract
Crude extract
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Phosphorylase
Phosphorylase
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cAMP
cAMP
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Protein Kinase A (PKA)
Protein Kinase A (PKA)
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Second messenger
Second messenger
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Particulate fraction
Particulate fraction
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First messenger
First messenger
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Glycogen degradation
Glycogen degradation
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Cryo-EM density map
Cryo-EM density map
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Adenylate cyclase (AC)
Adenylate cyclase (AC)
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Heterotrimeric G proteins
Heterotrimeric G proteins
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GTP binding
GTP binding
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GPCR
GPCR
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Conformational change
Conformational change
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Receptor-G protein complex
Receptor-G protein complex
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Signal amplification
Signal amplification
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Phosphoinositides
Phosphoinositides
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Inositol Triphosphate (IP3)
Inositol Triphosphate (IP3)
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Diacylglycerol (DAG)
Diacylglycerol (DAG)
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Calcium Ions (Ca2+)
Calcium Ions (Ca2+)
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Growth Factors
Growth Factors
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Signaling Molecules
Signaling Molecules
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Phospholipid binding
Phospholipid binding
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PLC isoforms
PLC isoforms
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PTEN
PTEN
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Pleckstrin homology (PH) domains
Pleckstrin homology (PH) domains
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FYVE domains
FYVE domains
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PI3K
PI3K
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Lipid phosphatases
Lipid phosphatases
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MAPK phosphatases
MAPK phosphatases
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Dual-specificity phosphatases (DSPs)
Dual-specificity phosphatases (DSPs)
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CDC25
CDC25
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Low Molecular Weight PTPs (LMWPTPs)
Low Molecular Weight PTPs (LMWPTPs)
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RNA polymerase II
RNA polymerase II
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Phosphorylation of Pol II CTD
Phosphorylation of Pol II CTD
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Asp-based catalysis
Asp-based catalysis
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Study Notes
Protein Kinases
- The human genome has approximately 518 protein kinases.
- About 10% of these kinases are pseudokinases.
- Most kinases have a 300 amino acid catalytic core.
- Kinases are grouped into 8 main classes.
Protein Phosphatases
- Eukaryotic cells have a variety of protein phosphatases.
- Phosphatases differ from kinases because they lack a defined sequence for dephosphorylation.
- Most phosphatases are in 4 distinct gene families.
Insulin Signaling
- Insulin is an extracellular messenger molecule that informs cells that glucose levels are high.
- Insulin receptors are protein tyrosine kinases with α & β chains linked by disulfide bonds.
- Insulin receptor activation leads to autophosphorylation and receptor activation.
- The activated receptor further phosphorylates insulin receptor substrates (IRS).
- IRS, in turn, provides binding sites for SH2 domain-containing signaling proteins.
- Following ligand binding and activation, the receptor phosphorylates itself at tyrosine residues in parts adjacent to the membrane and the carboxy-terminal tail.
- PI3K activated is a consequence of the binding of SH2 domains of PI 3-kinase & Grb2 to the activated receptor/IRS complex.
- PI3K then phosphorylates phosphoinositides.
- The products of PI3K phosphorylation, such as PI(3,4,5)P3, provide docking sites for PH domain proteins, such as PKB.
- The process leads to further downstream effects like protein synthesis, glucose uptake, and glycogen synthesis.
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