Podcast
Questions and Answers
Which type of protein-protein interaction involves stable complexes?
Which type of protein-protein interaction involves stable complexes?
- Reversible interactions
- Intramolecular interactions
- Permanent interactions (correct)
- Transient interactions
What do protein-protein interactions (PPIs) primarily facilitate within cells?
What do protein-protein interactions (PPIs) primarily facilitate within cells?
- DNA replication
- Nutrient absorption
- Energy production
- Communication and biochemical reactions (correct)
Homotypic protein-protein interactions specifically involve what?
Homotypic protein-protein interactions specifically involve what?
- Stable interactions only
- Temporary interactions
- Interactions between identical proteins (correct)
- Different types of proteins
Which of the following is an example of transient protein-protein interactions?
Which of the following is an example of transient protein-protein interactions?
Which process is NOT typically associated with protein-protein interactions?
Which process is NOT typically associated with protein-protein interactions?
What role do PPIs play in cellular structure?
What role do PPIs play in cellular structure?
What is a key difference between permanent and transient protein-protein interactions?
What is a key difference between permanent and transient protein-protein interactions?
Which statement about signal transduction is correct?
Which statement about signal transduction is correct?
What type of interactions occur in heterotypic protein-protein interactions?
What type of interactions occur in heterotypic protein-protein interactions?
Which binding force involves weak, non-specific attractions between nearby atoms?
Which binding force involves weak, non-specific attractions between nearby atoms?
What does the PDZ domain primarily interact with?
What does the PDZ domain primarily interact with?
What does a lower dissociation constant (Kd) indicate about a protein-protein interaction?
What does a lower dissociation constant (Kd) indicate about a protein-protein interaction?
Which protein interaction technique is best known for its high-throughput screening capability?
Which protein interaction technique is best known for its high-throughput screening capability?
What is the main advantage of using Co-Immunoprecipitation (Co-IP)?
What is the main advantage of using Co-Immunoprecipitation (Co-IP)?
Which structural feature is defined as a modular region that mediates interactions?
Which structural feature is defined as a modular region that mediates interactions?
What is a major consequence of mutations in protein binding surfaces?
What is a major consequence of mutations in protein binding surfaces?
What structural feature characterizes the WD40 domain?
What structural feature characterizes the WD40 domain?
Which type of residue is involved in ionic interactions within protein-protein binding?
Which type of residue is involved in ionic interactions within protein-protein binding?
Which technique provides values for binding constants (Kd) for protein interactions?
Which technique provides values for binding constants (Kd) for protein interactions?
What type of protein-protein interactions does X-ray Crystallography primarily determine?
What type of protein-protein interactions does X-ray Crystallography primarily determine?
What are hotspots in the context of protein-protein interactions?
What are hotspots in the context of protein-protein interactions?
Which of the following binding forces helps stabilize interactions between polar groups?
Which of the following binding forces helps stabilize interactions between polar groups?
Which technique is best suited for identifying components of large protein complexes?
Which technique is best suited for identifying components of large protein complexes?
Which domain recognizes phosphorylated tyrosines?
Which domain recognizes phosphorylated tyrosines?
What is the primary function of molecular docking in computational approaches?
What is the primary function of molecular docking in computational approaches?
How do viral pathogens typically disrupt host protein-protein interactions?
How do viral pathogens typically disrupt host protein-protein interactions?
What is a common consequence of mutations in tumor suppressor proteins like p53?
What is a common consequence of mutations in tumor suppressor proteins like p53?
Which therapeutic approach utilizes small molecules to block protein interactions relevant to diseases?
Which therapeutic approach utilizes small molecules to block protein interactions relevant to diseases?
What role does the SARS-CoV-2 spike protein play in the context of viral infections?
What role does the SARS-CoV-2 spike protein play in the context of viral infections?
Which of the following is NOT a method to therapeutically target protein-protein interactions?
Which of the following is NOT a method to therapeutically target protein-protein interactions?
What is a significant impact of protein aggregation in neurodegenerative diseases?
What is a significant impact of protein aggregation in neurodegenerative diseases?
Which AI-driven tool has become significant in predicting protein interactions?
Which AI-driven tool has become significant in predicting protein interactions?
What is a primary challenge in targeting protein-protein interactions (PPIs)?
What is a primary challenge in targeting protein-protein interactions (PPIs)?
Which of the following is an example of a small-molecule inhibitor that targets PPI?
Which of the following is an example of a small-molecule inhibitor that targets PPI?
What role do PROTACs play in targeting PPIs?
What role do PROTACs play in targeting PPIs?
How do peptidomimetics function in the context of PPI modulation?
How do peptidomimetics function in the context of PPI modulation?
What is the purpose of stabilizers in targeting weak PPIs?
What is the purpose of stabilizers in targeting weak PPIs?
Which of the following best describes the nature of many PPIs?
Which of the following best describes the nature of many PPIs?
What type of interactions can monoclonal antibodies block?
What type of interactions can monoclonal antibodies block?
Which of the following statements is true regarding the design of small molecules for PPI targeting?
Which of the following statements is true regarding the design of small molecules for PPI targeting?
What is the primary function of PROTACs in cancer therapy?
What is the primary function of PROTACs in cancer therapy?
What role does MDM2 play in the p53-MDM2 interaction?
What role does MDM2 play in the p53-MDM2 interaction?
Which small-molecule inhibitor restores p53 activity by blocking the p53-MDM2 interaction?
Which small-molecule inhibitor restores p53 activity by blocking the p53-MDM2 interaction?
What is the consequence of mutations in Ras or Raf proteins?
What is the consequence of mutations in Ras or Raf proteins?
What therapeutic challenge is associated with targeting the Ras-Raf signaling pathway?
What therapeutic challenge is associated with targeting the Ras-Raf signaling pathway?
In which context is Nutlin-3 particularly effective?
In which context is Nutlin-3 particularly effective?
What is the significance of understanding protein-protein interactions (PPIs) in signaling cascades?
What is the significance of understanding protein-protein interactions (PPIs) in signaling cascades?
What does the MAPK/ERK pathway primarily promote?
What does the MAPK/ERK pathway primarily promote?
What is the primary role of protein kinase C (PKC) in signaling cascades involving calcium and DAG?
What is the primary role of protein kinase C (PKC) in signaling cascades involving calcium and DAG?
Which physiological effect does increased cytosolic Ca²⁺ primarily contribute to?
Which physiological effect does increased cytosolic Ca²⁺ primarily contribute to?
Which of the following hormones is associated with tyrosine kinase signaling cascades?
Which of the following hormones is associated with tyrosine kinase signaling cascades?
How does PKC affect metabolic processes in the cell?
How does PKC affect metabolic processes in the cell?
What is one of the consequences of calcium's role in smooth muscle contraction?
What is one of the consequences of calcium's role in smooth muscle contraction?
What is the primary factor affecting how much hormone is released by endocrine glands?
What is the primary factor affecting how much hormone is released by endocrine glands?
Which hormone characteristic impacts its effectiveness at a target cell through its speed of breakdown?
Which hormone characteristic impacts its effectiveness at a target cell through its speed of breakdown?
What role does the receptor density on a target cell play in hormone response?
What role does the receptor density on a target cell play in hormone response?
How does downregulation of hormone receptors affect target cell sensitivity?
How does downregulation of hormone receptors affect target cell sensitivity?
What is the importance of intracellular signaling pathways in hormone action?
What is the importance of intracellular signaling pathways in hormone action?
Which factor determines whether a hormone is biologically active after secretion?
Which factor determines whether a hormone is biologically active after secretion?
What aspect of hormone behavior is influenced by post-receptor factors?
What aspect of hormone behavior is influenced by post-receptor factors?
What is the primary role of endocrine signaling?
What is the primary role of endocrine signaling?
Which type of signaling involves a cell releasing substances to affect its own function?
Which type of signaling involves a cell releasing substances to affect its own function?
Which of the following is an example of paracrine signaling?
Which of the following is an example of paracrine signaling?
What is a characteristic of endocrine signaling compared to other types of signaling?
What is a characteristic of endocrine signaling compared to other types of signaling?
In which scenario would a cell benefit from autocrine signaling?
In which scenario would a cell benefit from autocrine signaling?
Why are second messengers important in hormone signaling pathways?
Why are second messengers important in hormone signaling pathways?
Which statement accurately describes autocrine signaling?
Which statement accurately describes autocrine signaling?
What is the primary distinction between autocrine and paracrine signaling?
What is the primary distinction between autocrine and paracrine signaling?
What role does cGMP play in cellular signaling?
What role does cGMP play in cellular signaling?
What is a critical factor in the termination of cellular signals?
What is a critical factor in the termination of cellular signals?
What could be a potential consequence of dysregulation in the termination of hormonal signaling?
What could be a potential consequence of dysregulation in the termination of hormonal signaling?
Which of the following best describes the mechanism by which calcium and phosphatidylinositol act as second messengers?
Which of the following best describes the mechanism by which calcium and phosphatidylinositol act as second messengers?
Rapid signal termination in cellular signaling is important for what reason?
Rapid signal termination in cellular signaling is important for what reason?
Which hormone is NOT mentioned as utilizing calcium/phosphatidylinositol as a second messenger?
Which hormone is NOT mentioned as utilizing calcium/phosphatidylinositol as a second messenger?
What is one of the main effects of hyperactivity of cAMP pathways in certain cancers?
What is one of the main effects of hyperactivity of cAMP pathways in certain cancers?
Which term best describes the activation of guanylyl cyclase by hormones?
Which term best describes the activation of guanylyl cyclase by hormones?
Which of the following is NOT a characteristic of signal reversibility in cellular signaling?
Which of the following is NOT a characteristic of signal reversibility in cellular signaling?
What type of cellular response might result from inactivation defects in hormonal signaling?
What type of cellular response might result from inactivation defects in hormonal signaling?
What is the primary mechanism through which Group II hormones enact metabolic changes?
What is the primary mechanism through which Group II hormones enact metabolic changes?
Which of the following hormone types requires transport proteins in the bloodstream?
Which of the following hormone types requires transport proteins in the bloodstream?
What defines the plasma half-life of Group I hormones compared to Group II hormones?
What defines the plasma half-life of Group I hormones compared to Group II hormones?
Which cellular action is specifically associated with insulin among Group II hormones?
Which cellular action is specifically associated with insulin among Group II hormones?
What is the solubility characteristic of Group II hormones?
What is the solubility characteristic of Group II hormones?
What outcome arises from the convergence of effects from Group I and Group II hormones?
What outcome arises from the convergence of effects from Group I and Group II hormones?
Which type of receptor is typically associated with Group I hormones?
Which type of receptor is typically associated with Group I hormones?
What role does cAMP play in hormone signaling mechanisms?
What role does cAMP play in hormone signaling mechanisms?
Which of the following hormones would be classified under Group I hormones?
Which of the following hormones would be classified under Group I hormones?
How do changes in protein synthesis relate to hormone action?
How do changes in protein synthesis relate to hormone action?
Hormones stimulate guanylyl cyclase activity, leading to increased levels of cAMP in the cell.
Hormones stimulate guanylyl cyclase activity, leading to increased levels of cAMP in the cell.
Enzymes like phosphatases are crucial for the initiation of signal transduction pathways.
Enzymes like phosphatases are crucial for the initiation of signal transduction pathways.
Excessive cellular responses due to overactivation can be caused by hyperactivity of cGMP pathways in certain diseases.
Excessive cellular responses due to overactivation can be caused by hyperactivity of cGMP pathways in certain diseases.
Calcium acts as a second messenger by activating phospholipase C in response to specific hormones.
Calcium acts as a second messenger by activating phospholipase C in response to specific hormones.
Signal termination mechanisms ensure that signaling pathways are permanently activated.
Signal termination mechanisms ensure that signaling pathways are permanently activated.
CAMP activates protein kinases, leading to the synthesis of target proteins.
CAMP activates protein kinases, leading to the synthesis of target proteins.
Group I hormones are hydrophilic and include steroids and thyroid hormones.
Group I hormones are hydrophilic and include steroids and thyroid hormones.
The plasma half-life of Group II hormones is typically long, lasting hours to days.
The plasma half-life of Group II hormones is typically long, lasting hours to days.
Protein translocation, such as GLUT4 in insulin action, is a mechanism used exclusively by Group I hormones.
Protein translocation, such as GLUT4 in insulin action, is a mechanism used exclusively by Group I hormones.
Group II hormones circulate freely in plasma and do not require transport proteins in blood.
Group II hormones circulate freely in plasma and do not require transport proteins in blood.
The effects of both Group I and Group II hormones converge into a coordinated response to maintain homeostasis.
The effects of both Group I and Group II hormones converge into a coordinated response to maintain homeostasis.
Intracellular receptors for Group I hormones are located only in the cytoplasm.
Intracellular receptors for Group I hormones are located only in the cytoplasm.
The mechanisms of hormone action for lipid-soluble hormones do not involve synthesis of specific proteins that mediate biological responses.
The mechanisms of hormone action for lipid-soluble hormones do not involve synthesis of specific proteins that mediate biological responses.
Notch signaling is an example of paracrine signaling involved in cell differentiation.
Notch signaling is an example of paracrine signaling involved in cell differentiation.
Juxtacrine signaling requires direct cell-to-cell contact with signaling molecules remaining bound to the cytoplasm.
Juxtacrine signaling requires direct cell-to-cell contact with signaling molecules remaining bound to the cytoplasm.
Group I hormones are characterized by their lipid-soluble nature, allowing them to bind to intracellular receptors.
Group I hormones are characterized by their lipid-soluble nature, allowing them to bind to intracellular receptors.
Water-soluble hormones, such as glucagon, diffuse through the plasma membrane easily due to their lipophilic properties.
Water-soluble hormones, such as glucagon, diffuse through the plasma membrane easily due to their lipophilic properties.
Lipid-soluble hormones form a hormone-receptor complex in the cytoplasm or nucleus, influencing gene expression by binding to DNA.
Lipid-soluble hormones form a hormone-receptor complex in the cytoplasm or nucleus, influencing gene expression by binding to DNA.
Adenylyl cyclase is stimulated by water-soluble hormones through their binding to G-protein-coupled receptors (GPCRs).
Adenylyl cyclase is stimulated by water-soluble hormones through their binding to G-protein-coupled receptors (GPCRs).
The main types of Group II hormones include steroids and thyroid hormones.
The main types of Group II hormones include steroids and thyroid hormones.
Phosphorylation of proteins is a mechanism solely associated with Group I hormones.
Phosphorylation of proteins is a mechanism solely associated with Group I hormones.
The enzyme phosphodiesterase converts AMP back into cAMP to prolong the signal.
The enzyme phosphodiesterase converts AMP back into cAMP to prolong the signal.
Dephosphorylation of target proteins is mediated by protein kinases.
Dephosphorylation of target proteins is mediated by protein kinases.
As cAMP levels increase, the regulatory subunits of Protein Kinase A (PKA) dissociate from its catalytic subunits, activating PKA.
As cAMP levels increase, the regulatory subunits of Protein Kinase A (PKA) dissociate from its catalytic subunits, activating PKA.
The hydrolysis of GTP into GDP by the G-protein α-subunit activates the G-protein.
The hydrolysis of GTP into GDP by the G-protein α-subunit activates the G-protein.
Atrial natriuretic peptide (ANP) is an example of a hormone that binds to cell surface receptors using cAMP as the second messenger.
Atrial natriuretic peptide (ANP) is an example of a hormone that binds to cell surface receptors using cAMP as the second messenger.
Inhibition of adenylyl cyclase ceases the production of cGMP.
Inhibition of adenylyl cyclase ceases the production of cGMP.
Phosphodiesterase enzymes play a crucial role in terminating cAMP signaling.
Phosphodiesterase enzymes play a crucial role in terminating cAMP signaling.
The reassembly of G-protein subunits occurs when the α-subunit is in its GDP-bound form.
The reassembly of G-protein subunits occurs when the α-subunit is in its GDP-bound form.
Protein phosphatases are responsible for adding phosphate groups to target proteins.
Protein phosphatases are responsible for adding phosphate groups to target proteins.
Activation of PKA is facilitated by increased levels of cAMP.
Activation of PKA is facilitated by increased levels of cAMP.
Androgens, estrogens, and progestins are types of thyroid hormones.
Androgens, estrogens, and progestins are types of thyroid hormones.
Calcitriol is responsible for regulating calcium and phosphate homeostasis.
Calcitriol is responsible for regulating calcium and phosphate homeostasis.
CAMP is produced by the activation of the enolase enzyme.
CAMP is produced by the activation of the enolase enzyme.
The trimeric G-protein consists of alpha, beta, and delta subunits.
The trimeric G-protein consists of alpha, beta, and delta subunits.
Ligand binding induces a conformational change in the G-Protein Coupled Receptor (GPCR).
Ligand binding induces a conformational change in the G-Protein Coupled Receptor (GPCR).
Thyroid hormones primarily influence reproduction and secondary sexual characteristics.
Thyroid hormones primarily influence reproduction and secondary sexual characteristics.
Adenylyl cyclase becomes active when the G-protein is in an inactive state.
Adenylyl cyclase becomes active when the G-protein is in an inactive state.
Glucagon is an example of a hormone that binds to cell surface receptors and utilizes cAMP.
Glucagon is an example of a hormone that binds to cell surface receptors and utilizes cAMP.
Protein kinases are activated by increased levels of cyclic AMP (cAMP).
Protein kinases are activated by increased levels of cyclic AMP (cAMP).
Calcitonin is a lipophilic hormone that passes through the cell membrane.
Calcitonin is a lipophilic hormone that passes through the cell membrane.
Flashcards
What are Protein-Protein Interactions (PPIs)?
What are Protein-Protein Interactions (PPIs)?
Physical contacts between two or more protein molecules, driven by biochemical forces.
Why are PPIs important?
Why are PPIs important?
PPIs are crucial for various cellular functions, from communication and structure to biochemical reactions.
How do PPIs play a role in signal transduction?
How do PPIs play a role in signal transduction?
PPIs help in transmitting signals within and between cells, often involving receptor-ligand binding.
How are PPIs involved in enzyme-substrate binding?
How are PPIs involved in enzyme-substrate binding?
Signup and view all the flashcards
What is the role of PPIs in structural assembly?
What is the role of PPIs in structural assembly?
Signup and view all the flashcards
What is the difference between permanent and transient PPIs?
What is the difference between permanent and transient PPIs?
Signup and view all the flashcards
Differentiate between homotypic and heterotypic interactions.
Differentiate between homotypic and heterotypic interactions.
Signup and view all the flashcards
What factors influence PPIs?
What factors influence PPIs?
Signup and view all the flashcards
SH2 domain
SH2 domain
Signup and view all the flashcards
PDZ domain
PDZ domain
Signup and view all the flashcards
WD40 domain
WD40 domain
Signup and view all the flashcards
Yeast Two-Hybrid (Y2H)
Yeast Two-Hybrid (Y2H)
Signup and view all the flashcards
Co-Immunoprecipitation (Co-IP)
Co-Immunoprecipitation (Co-IP)
Signup and view all the flashcards
X-ray Crystallography
X-ray Crystallography
Signup and view all the flashcards
Surface Plasmon Resonance (SPR)
Surface Plasmon Resonance (SPR)
Signup and view all the flashcards
Mass Spectrometry
Mass Spectrometry
Signup and view all the flashcards
Heterotypic interaction
Heterotypic interaction
Signup and view all the flashcards
Binding force
Binding force
Signup and view all the flashcards
Ionic interaction
Ionic interaction
Signup and view all the flashcards
Hydrophobic interaction
Hydrophobic interaction
Signup and view all the flashcards
Binding affinity
Binding affinity
Signup and view all the flashcards
Dissociation constant (Kd)
Dissociation constant (Kd)
Signup and view all the flashcards
Domain
Domain
Signup and view all the flashcards
Interface
Interface
Signup and view all the flashcards
What is the role of disrupted PPIs in cancer?
What is the role of disrupted PPIs in cancer?
Signup and view all the flashcards
How do PPIs contribute to neurodegenerative diseases?
How do PPIs contribute to neurodegenerative diseases?
Signup and view all the flashcards
How do pathogens use disrupted PPIs to cause infections?
How do pathogens use disrupted PPIs to cause infections?
Signup and view all the flashcards
How does HIV hijack host PPIs?
How does HIV hijack host PPIs?
Signup and view all the flashcards
How does SARS-CoV-2 utilize PPIs to enter cells?
How does SARS-CoV-2 utilize PPIs to enter cells?
Signup and view all the flashcards
How do small-molecule inhibitors target disease pathways?
How do small-molecule inhibitors target disease pathways?
Signup and view all the flashcards
What are peptidomimetics and how do they work?
What are peptidomimetics and how do they work?
Signup and view all the flashcards
How do monoclonal antibodies target PPIs?
How do monoclonal antibodies target PPIs?
Signup and view all the flashcards
Small-Molecule Inhibitors
Small-Molecule Inhibitors
Signup and view all the flashcards
Stabilizers for Weak PPIs
Stabilizers for Weak PPIs
Signup and view all the flashcards
Peptidomimetics
Peptidomimetics
Signup and view all the flashcards
Antibodies as PPI Modulators
Antibodies as PPI Modulators
Signup and view all the flashcards
PROTACs
PROTACs
Signup and view all the flashcards
Protein Degraders
Protein Degraders
Signup and view all the flashcards
What makes PPI binding sites challenging?
What makes PPI binding sites challenging?
Signup and view all the flashcards
Why are transient PPIs difficult to target?
Why are transient PPIs difficult to target?
Signup and view all the flashcards
What are PROTACs?
What are PROTACs?
Signup and view all the flashcards
How are PROTACs used in cancer therapy?
How are PROTACs used in cancer therapy?
Signup and view all the flashcards
What is the role of p53 and MDM2 in cancer?
What is the role of p53 and MDM2 in cancer?
Signup and view all the flashcards
How does Nutlin-3 work in cancer therapy?
How does Nutlin-3 work in cancer therapy?
Signup and view all the flashcards
What is the role of Ras and Raf in cancer?
What is the role of Ras and Raf in cancer?
Signup and view all the flashcards
How does Vemurafenib work in melanoma treatment?
How does Vemurafenib work in melanoma treatment?
Signup and view all the flashcards
What is a challenge in targeting the Ras-Raf pathway?
What is a challenge in targeting the Ras-Raf pathway?
Signup and view all the flashcards
Why is targeting protein-protein interactions in cancer therapy complex?
Why is targeting protein-protein interactions in cancer therapy complex?
Signup and view all the flashcards
Hormone Synthesis & Secretion
Hormone Synthesis & Secretion
Signup and view all the flashcards
Inactive Hormone Activation
Inactive Hormone Activation
Signup and view all the flashcards
Hormone Clearance Rate
Hormone Clearance Rate
Signup and view all the flashcards
Receptor Occupancy & Activity
Receptor Occupancy & Activity
Signup and view all the flashcards
Receptor Regulation
Receptor Regulation
Signup and view all the flashcards
Post-Receptor Factors
Post-Receptor Factors
Signup and view all the flashcards
Factors Affecting Hormone Response
Factors Affecting Hormone Response
Signup and view all the flashcards
Endocrine Signaling
Endocrine Signaling
Signup and view all the flashcards
Paracrine Signaling
Paracrine Signaling
Signup and view all the flashcards
Autocrine Signaling
Autocrine Signaling
Signup and view all the flashcards
Signal Transduction
Signal Transduction
Signup and view all the flashcards
Second Messengers
Second Messengers
Signup and view all the flashcards
Hormone-Receptor Binding
Hormone-Receptor Binding
Signup and view all the flashcards
Recognition
Recognition
Signup and view all the flashcards
Effects
Effects
Signup and view all the flashcards
Signal Generation
Signal Generation
Signup and view all the flashcards
Group I Hormones
Group I Hormones
Signup and view all the flashcards
Group II Hormones
Group II Hormones
Signup and view all the flashcards
Intracellular Receptor Action
Intracellular Receptor Action
Signup and view all the flashcards
Plasma Membrane Receptor Action
Plasma Membrane Receptor Action
Signup and view all the flashcards
Integrated Hormone Response
Integrated Hormone Response
Signup and view all the flashcards
cAMP
cAMP
Signup and view all the flashcards
Phosphorylation
Phosphorylation
Signup and view all the flashcards
Protein Translocation
Protein Translocation
Signup and view all the flashcards
Metabolic Changes
Metabolic Changes
Signup and view all the flashcards
Homeostasis
Homeostasis
Signup and view all the flashcards
Calcium and Muscle Contraction
Calcium and Muscle Contraction
Signup and view all the flashcards
Calcium and Secretion
Calcium and Secretion
Signup and view all the flashcards
PKC and Metabolism
PKC and Metabolism
Signup and view all the flashcards
Growth Hormone/Prolactin Signaling
Growth Hormone/Prolactin Signaling
Signup and view all the flashcards
Insulin and Receptor Tyrosine Kinase (RTK)
Insulin and Receptor Tyrosine Kinase (RTK)
Signup and view all the flashcards
cGMP as a Second Messenger
cGMP as a Second Messenger
Signup and view all the flashcards
Reversibility of Signaling Pathways
Reversibility of Signaling Pathways
Signup and view all the flashcards
Enzymes for Signal Termination
Enzymes for Signal Termination
Signup and view all the flashcards
Importance of Signal Termination
Importance of Signal Termination
Signup and view all the flashcards
Overstimulation and Disease
Overstimulation and Disease
Signup and view all the flashcards
Inactivation Defects and Disease
Inactivation Defects and Disease
Signup and view all the flashcards
Calcium/Phosphatidylinositol Signaling
Calcium/Phosphatidylinositol Signaling
Signup and view all the flashcards
PLC and Second Messengers
PLC and Second Messengers
Signup and view all the flashcards
Calcium as a Second Messenger
Calcium as a Second Messenger
Signup and view all the flashcards
DAG and Protein Kinase C (PKC)
DAG and Protein Kinase C (PKC)
Signup and view all the flashcards
Lipid-Soluble Hormones
Lipid-Soluble Hormones
Signup and view all the flashcards
Water-Soluble Hormones
Water-Soluble Hormones
Signup and view all the flashcards
G-Protein-Coupled Receptor (GPCR)
G-Protein-Coupled Receptor (GPCR)
Signup and view all the flashcards
Calcium/Phosphatidylinositol Signaling Pathway
Calcium/Phosphatidylinositol Signaling Pathway
Signup and view all the flashcards
What is Phospholipase C (PLC)?
What is Phospholipase C (PLC)?
Signup and view all the flashcards
What is Diacylglycerol (DAG)?
What is Diacylglycerol (DAG)?
Signup and view all the flashcards
What is Inositol Triphosphate (IP3)?
What is Inositol Triphosphate (IP3)?
Signup and view all the flashcards
What is the role of Calcium in cellular signaling?
What is the role of Calcium in cellular signaling?
Signup and view all the flashcards
Termination of cAMP Signal
Termination of cAMP Signal
Signup and view all the flashcards
Release of Hormone from Receptor
Release of Hormone from Receptor
Signup and view all the flashcards
Dephosphorylation of Target Proteins
Dephosphorylation of Target Proteins
Signup and view all the flashcards
Degradation of cAMP into AMP
Degradation of cAMP into AMP
Signup and view all the flashcards
Inactivation of Protein Kinase A (PKA)
Inactivation of Protein Kinase A (PKA)
Signup and view all the flashcards
Hydrolysis of GTP into GDP
Hydrolysis of GTP into GDP
Signup and view all the flashcards
Reassembly of G-Protein Subunits
Reassembly of G-Protein Subunits
Signup and view all the flashcards
Inactivation of Adenylyl Cyclase
Inactivation of Adenylyl Cyclase
Signup and view all the flashcards
What are sex hormones and what do they control?
What are sex hormones and what do they control?
Signup and view all the flashcards
What are Thyroid Hormones and what do they regulate?
What are Thyroid Hormones and what do they regulate?
Signup and view all the flashcards
What does calcitriol do?
What does calcitriol do?
Signup and view all the flashcards
What is the role of Retinoic Acid?
What is the role of Retinoic Acid?
Signup and view all the flashcards
Describe how hormones in Group II work.
Describe how hormones in Group II work.
Signup and view all the flashcards
Explain the resting state of a cell before a Group II hormone binds.
Explain the resting state of a cell before a Group II hormone binds.
Signup and view all the flashcards
Describe how a Group II hormone activates the G-protein and adenylyl cyclase.
Describe how a Group II hormone activates the G-protein and adenylyl cyclase.
Signup and view all the flashcards
Explain the role of cAMP in Group II hormone signaling.
Explain the role of cAMP in Group II hormone signaling.
Signup and view all the flashcards
How do Group I hormones work?
How do Group I hormones work?
Signup and view all the flashcards
Explain the integrated response of Group I and Group II hormones.
Explain the integrated response of Group I and Group II hormones.
Signup and view all the flashcards
Study Notes
Protein-Protein Interactions (PPIs)
- Protein-protein interactions (PPIs) are the physical contacts between two or more protein molecules.
- These interactions are driven by biochemical forces.
- PPIs are crucial for all cellular processes, facilitating communication, maintaining structural integrity, and driving biochemical reactions.
- PPIs occur in various ways, including some being permanent (e.g., hemoglobin subunits) and others being temporary and dynamic.
Relevance of PPIs
- Signal Transduction: PPIs transmit signals within and between cells (e.g., receptor-ligand binding).
- Enzyme-Substrate Binding: PPIs facilitate specific interactions for catalyzing reactions, such as kinases interacting with their substrates.
- Structural Assembly: PPIs form macromolecular complexes, including the cytoskeleton and ribosomes.
Types of PPIs
- Permanent vs. Transient: Some interactions are permanent and stable, like hemoglobin subunits, while others are transient and involve temporary interactions.
- Homotypic vs. Heterotypic: Homotypic interactions involve identical proteins, such as dimerization of transcription factors. Heterotypic interactions involve the interaction between different proteins, like antigen-antibody binding.
Biophysical Basis of PPIs
- Binding Forces: PPIs are stabilized by various forces, including hydrogen bonding (polar interactions), van der Waals forces (non-specific attraction between nearby atoms), ionic interactions (electrostatic interactions between charged residues), and hydrophobic interactions (non-polar residues clustering to avoid water).
- Disulfide linkages: Disulfide bridges are formed between cysteine groups, contributing to the overall stability of the complex.
- Images of different types of bonds help visualize the interactive protein shapes
Binding Affinity and Specificity
- Dissociation Constant (Kd): The dissociation constant (Kd) measures the strength of a PPI. A lower Kd indicates stronger affinity.
- Effect of Mutations: Mutations can disrupt binding interfaces, alter protein shape, and affect interaction strengths, sometimes enhancing or weakening interactions.
Structural Features
- Domains: Protein domains are modular regions involved in mediating interactions, such as SH2 (phosphorylated tyrosines) domains, PDZ (short peptide motifs), WD40 (multi-protein complexes).
- Interfaces and Hotspots: Interaction interfaces are contact regions between proteins, often complementary in shape and charge. Hotspots are key residues within these interfaces crucial for binding, often targeting these for drug design. Illustrated structure images may be help in understanding these concepts.
Experimental Methods for Studying PPIs
- Yeast Two-Hybrid (Y2H): Used for detecting binary interactions using a reporter gene in yeast.
- Co-Immunoprecipitation (Co-IP): Used to pull down protein complexes using specific antibodies and validate direct or indirect interactions.
- X-ray Crystallography: Determines the atomic-level 3D structures of PPIs.
- NMR Spectroscopy: Resolves the structures of flexible or dynamic PPIs in solution
- Surface Plasmon Resonance (SPR): Measures real-time binding kinetics and affinity.
- Mass Spectrometry: Identifies components of large protein complexes.
Computational Approaches
- Molecular Docking and Dynamics: Used to simulate interactions between protein structures to predict binding modes.
- AI-Driven Prediction Models: Tools like AlphaFold predict interaction sites and structures, enabling predictions from uncharacterized proteins.
PPIs in Diseases
- Cancer: Mutations and disruptions in tumor suppressor proteins and hyperactive oncogenic pathways impact PPIs. Examples include p53-MDM2 interaction disruptions.
- Neurodegenerative Diseases: Misfolded proteins disrupt PPIs, causing disease. Examples of these include tau in Alzheimer's and α-synuclein in Parkinson's.
- Infections: Bacterial and viral pathogens disrupt or mimic host PPIs to evade the immune system. Examples include HIV interactions with host transcription machinery or SARS-CoV-2 interaction with ACE2 receptors, facilitating entry.
- Viral Hijacking of Host PPIs: Viruses exploit host PPIs for their own replication.
Therapeutic Targeting of PPIs
- Small-Molecule Inhibitors: Small molecules block specific PPI interactions. Examples include Nutlin-3, which blocks p53-MDM2 interaction and small molecule inhibitors targeting mutant BRAF.
- Peptidomimetics: Mimetics mimic the natural interactions, inhibiting relevant PPIs. Examples include BH3 mimetics.
- Monoclonal Antibodies: Target extracellular PPIs. Examples include immune checkpoint inhibitors.
- Protein Degraders (PROTACS): Induce the degradation of proteins disrupting PPIs to restore normal function. Example includes those targeting BRD4.
Challenges in Targeting PPIs
- Large, Flat Binding Surfaces: PPI interfaces are often extensive and lack specific pockets, making targeting challenging.
- Transient Interactions: Identifying and targeting transient interactions are often difficult.
Approaches to Target PPIs
- Small Molecule Inhibitors: Targeting specific regions within the interaction interface, often exploiting protein hotspots. Small molecules often target these regions.
- Stabilizers for Weak PPIs: Enhancing or stabilizing interactions to restore normal function, such as stabilizing protein folding complexes.
- Peptidomimetics: Mimic natural interaction motifs for inhibiting disease-relevant PPIs.
- Antibodies: Modulate or block extracellular PPIs; monoclonal antibodies can target specific interactions.
- Protein Degraders (PROTACS): Degrade proteins disrupting PPIs to restore normal function. PROTACs are chimeric molecules mediating the targeting and degradation of interacting proteins.
Case Studies
- p53-MDM2 Interaction in Cancer Therapy: Small molecules like Nutlin-3 block this interaction, restoring p53 activity to combat cancer.
- Ras-Raf Signaling in MAPK Pathways: Therapies are employed for reactivation pathway targeting. Vemurafenib targets mutant BRAF in melanoma but faces challenges like potential reactivation of BRAF pathway.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on protein-protein interactions (PPIs) and their significance in cellular functions. This quiz covers the types, characteristics, and roles of PPIs, along with key concepts like transient and stable complexes. Challenge yourself with questions about signal transduction and binding forces involved in these critical interactions.
