GPCR Function and Significance Quiz

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Questions and Answers

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?

  • 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?

  • 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?

<p>Enzymes (D)</p> Signup and view all the answers

What is the function of olfactory sensory neurons in vertebrates?

<p>They detect and transmit signals related to smell. (A)</p> Signup and view all the answers

What is the significance of the similarity between the odorant-binding pocket in OR51E2 and the binding pockets of other class A GPCRs?

<p>It indicates that these receptors share similar ligand binding properties. (A), It suggests a common evolutionary origin for these receptors. (B)</p> Signup and view all the answers

What is the role of Gαs in the activation of OR51E2?

<p>Gαs activates adenylyl cyclase, which converts ATP to cAMP. (C)</p> Signup and view all the answers

What is the likely consequence of a mutation in the transmembrane domain of an odorant receptor?

<p>All of the above. (D)</p> Signup and view all the answers

What is the function of adenylate cyclase in the context of the provided text?

<p>Adenylate cyclase catalyzes the synthesis of cAMP from ATP. (B)</p> Signup and view all the answers

What is the primary function of the transmembrane domain bundle (TM) in the AC9-Gαs complex?

<p>The TM domain is responsible for transmitting the signal across the plasma membrane. (A)</p> Signup and view all the answers

What does the term 'heterotrimeric' refer to in the context of G proteins?

<p>The G protein is composed of three different subunits, α, β, and γ. (C)</p> Signup and view all the answers

The text mentions a change in conformation in the receptor molecule. What does this change in conformation directly lead to?

<p>The release of GDP from the Gα subunit. (E)</p> Signup and view all the answers

Which of the following statements accurately describes the role of the α subunit in the G protein?

<p>The α subunit binds to guanine nucleotides and undergoes conformational changes upon activation. (C)</p> Signup and view all the answers

What is the significance of the lipid chains attached to the α and γ subunits of the G protein?

<p>They anchor the G protein to the plasma membrane. (D)</p> Signup and view all the answers

The activation of a single receptor can lead to the activation of multiple G protein molecules. This phenomenon is referred to as:

<p>Signal amplification. (D)</p> Signup and view all the answers

Based on the content, what can be inferred about the role of the AC9-Gαs complex in cellular signaling?

<p>The complex is involved in the synthesis and regulation of cAMP. (C)</p> Signup and view all the answers

What is the primary function of phospholipids in cell membranes?

<p>To provide structural integrity and impermeability (B)</p> Signup and view all the answers

Which of the following is NOT a lipid-derived second messenger?

<p>cGMP (C)</p> Signup and view all the answers

What is a growth factor?

<p>A naturally occurring substance that stimulates cellular growth and differentiation (B)</p> Signup and view all the answers

How do growth factors typically act on their target cells?

<p>By binding to specific receptors on the cell surface and triggering a signaling cascade (D)</p> Signup and view all the answers

What is the significance of the increase in phosphoinositides levels in cells treated with growth factors?

<p>It suggests that a signaling pathway involving phosphoinositides is activated (A)</p> Signup and view all the answers

Which of the following statements about phospholipids is TRUE?

<p>Phospholipids are essential components of cell membranes and signaling pathways (A)</p> Signup and view all the answers

What is the most likely outcome of a mutation that prevents the production of a specific growth factor?

<p>The cell will stop responding to growth factors (B)</p> Signup and view all the answers

Why are growth factors important for cellular development?

<p>They regulate cell division and specialization (B)</p> Signup and view all the answers

What is the role of cyclic AMP (cAMP) in the breakdown of glycogen?

<p>cAMP activates a protein kinase which phosphorylates phosphorylase, leading to glycogen breakdown. (B)</p> Signup and view all the answers

What is the significance of the 'substance' identified by Sutherland as cyclic AMP?

<p>It acts as a second messenger, transmitting the signal from the hormone to phosphorylase. (B)</p> Signup and view all the answers

In the context of the described experiment, why was the hormone-treated particulate fraction washed and the wash added to the supernatant?

<p>To isolate the substance released by the particulate fraction upon hormone treatment. (B)</p> Signup and view all the answers

What is the primary function of the protein kinase activated by cAMP, in the context of glycogen breakdown?

<p>Bind to and activate phosphorylase, initiating glycogen breakdown. (A)</p> Signup and view all the answers

Which of the following statements accurately describes the role of a second messenger in cell signaling?

<p>Second messengers act as intermediaries, relaying the signal from the hormone to intracellular targets. (C)</p> Signup and view all the answers

What is the key difference between the hormone and the second messenger (cAMP)?

<p>The hormone binds to the cell surface receptor, while cAMP acts inside the cell. (B)</p> Signup and view all the answers

How does the activation of phosphorylase lead to glycogen breakdown?

<p>By directly breaking down glycogen into glucose monomers. (C)</p> Signup and view all the answers

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?

<p>The wash contained a substance released by the particulate fraction that, upon hormone binding, activated phosphorylase. (C)</p> Signup and view all the answers

What is the specific phosphoinositide that FYVE and PX domains bind to?

<p>PI-3-P (A)</p> Signup and view all the answers

What is the role of the PLC isoforms in phospholipid binding?

<p>They recognize and bind to specific phosphoinositides and diacylglycerol. (C)</p> Signup and view all the answers

Which of the following domains is NOT involved in phosphoinositide recognition?

<p>EF (A)</p> Signup and view all the answers

What is the term used for the family of enzymes that catalyze the phosphorylation of the 3-position of the inositol ring in phosphoinositides?

<p>PI3K (B)</p> Signup and view all the answers

Which phosphoinositide is specifically recognized by pleckstrin homology (PH) domains?

<p>All of the above (D)</p> Signup and view all the answers

Which of the following is true about the interaction of FYVE and PX domains with membranes?

<p>They interact with both polar and hydrophobic regions of the membrane. (C)</p> Signup and view all the answers

What is the role of enzymes like PTEN and SHIP in PI metabolism?

<p>They act as lipid phosphatases, removing phosphate groups from phosphoinositides. (D)</p> Signup and view all the answers

What is the primary function of phosphoinositide kinases in PI metabolism?

<p>They add phosphate groups to phosphoinositides. (D)</p> Signup and view all the answers

Which of the following enzymes are involved in the dephosphorylation of key tyrosine residues (pY) on cyclin-dependent kinases (cdks)?

<p>CDC25s (C)</p> Signup and view all the answers

What is the significance of the CX5R signature in the context of dual-specificity phosphatases (DSPs)?

<p>It indicates that DSPs can dephosphorylate both tyrosine and serine/threonine residues. (D)</p> Signup and view all the answers

Which type of phosphatase utilizes Asp-based catalysis?

<p>A fourth family of phosphatases (B)</p> Signup and view all the answers

What is the role of FCP/SCP in the regulation of RNA polymerase II?

<p>FCP/SCP dephosphorylates specific serine residues on the C-terminal domain of RNA polymerase II. (D)</p> Signup and view all the answers

What is the primary role of the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II?

<p>It regulates the elongation of nascent RNA transcripts. (C)</p> Signup and view all the answers

What is the primary function of LMWPTPs?

<p>They dephosphorylate phosphoinositides, mRNA, and serine/threonine residues. (A)</p> Signup and view all the answers

Which of the following statements is TRUE about the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II?

<p>It involves multistep phosphorylation at Ser2, Ser5, and Ser7. (D)</p> Signup and view all the answers

Why are dual-specificity phosphatases (DSPs) known as a diverse bunch?

<p>They can dephosphorylate a wide range of substrates, including phosphoinositides, mRNA, and even serine and threonine residues. (D)</p> Signup and view all the answers

Flashcards

G Protein-Coupled Receptors (GPCRs)

Membrane proteins that interact with G proteins and have 7 transmembrane helices.

Natural ligands

Molecules like hormones and neurotransmitters that bind to GPCRs to activate them.

Olfactory Receptors (ORs)

A subtype of GPCRs that detect odorants in the sensory neurons.

C.elegans GPCRs

The nematode C.elegans encodes around 1000 GPCRs in its genome.

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GPCR drug target

GPCRs are the most common target for drug discovery in the pharmaceutical industry.

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Inactivating mutations

Genetic changes in GPCRs linked to over 30 human diseases.

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Transmembrane helices

Structural features of GPCRs that span the cell membrane.

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cAMP in GPCR signaling

Cyclo-AMP (cAMP) is a second messenger involved in transmitting signals from GPCRs.

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Crude extract

A preparation of broken-cell components for experiments.

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Phosphorylase

An enzyme activated by cAMP that plays a role in glycogen degradation.

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cAMP

Cyclic adenosine monophosphate, a second messenger involved in cellular signaling.

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Protein Kinase A (PKA)

An enzyme activated by cAMP that phosphorylates various substrates.

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Second messenger

Molecules like cAMP that mediate and amplify cellular responses from first messengers.

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Particulate fraction

The cell component containing membranes that release signaling molecules.

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First messenger

A signaling molecule (like a hormone) that binds to a receptor on the cell surface.

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Glycogen degradation

The process of breaking down glycogen into glucose, activated by phosphorylase.

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Cryo-EM density map

A 3D structural representation of the AC9-Gαs complex.

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Adenylate cyclase (AC)

An enzyme that converts ATP to cAMP.

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Heterotrimeric G proteins

Proteins composed of three subunits: α, β, and γ.

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GTP binding

Replacement of GDP with GTP that activates G proteins.

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GPCR

G protein-coupled receptors that respond to ligands.

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Conformational change

Alteration in the shape of a protein upon activation.

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Receptor-G protein complex

Complex formed when GPCR binds to G protein.

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Signal amplification

Process where one active receptor activates multiple G proteins.

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Phosphoinositides

Lipids that act as second messengers in cellular signaling pathways.

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Inositol Triphosphate (IP3)

A second messenger that triggers the release of calcium ions from the endoplasmic reticulum.

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Diacylglycerol (DAG)

A second messenger derived from phospholipids that activates protein kinase C (PKC).

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Calcium Ions (Ca2+)

An important second messenger that regulates various cellular functions.

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Growth Factors

Naturally occurring substances that stimulate cell growth, proliferation, healing, and differentiation.

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Signaling Molecules

Substances that convey instructions or information between cells.

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Phospholipid binding

The interaction of proteins with phospholipid molecules in membranes.

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PLC isoforms

Different forms of phospholipase C that hydrolyze phosphoinositides.

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PTEN

A lipid phosphatase that removes phosphate from PIP3, involved in signaling pathways.

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Pleckstrin homology (PH) domains

Protein domains that bind specifically to phosphoinositides like PtdIns(4,5)P2.

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FYVE domains

Protein domains that bind specifically to PtdIns3P, involved in endosomal trafficking.

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PI3K

A family of enzymes that phosphorylate the 3-position of phosphoinositides.

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Lipid phosphatases

Enzymes that remove phosphate groups from lipids, regulating cellular signals.

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MAPK phosphatases

Enzymes that deactivate MAP kinases by removing phosphate groups.

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Dual-specificity phosphatases (DSPs)

A family of phosphatases that can dephosphorylate multiple substrates like mRNA and serines.

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CDC25

A class of phosphatases that dephosphorylate key tyrosine residues on cyclin-dependent kinases (cdks).

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Low Molecular Weight PTPs (LMWPTPs)

A class of phosphatases involved in various cellular processes, often smaller in size.

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RNA polymerase II

An enzyme that transcribes DNA into mRNA, snRNA, and microRNAs, regulated by phosphorylation.

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Phosphorylation of Pol II CTD

Process involving the addition of phosphate groups to the C-terminal domain of RNA polymerase II, influencing transcript maturation.

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Asp-based catalysis

A mechanism employed by some phosphatases using aspartic acid in the catalytic process.

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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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