Biochemistry Chapter on Receptor Interactions

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Questions and Answers

Which type of receptors are primarily associated with structural proteins on cell surfaces that respond to ligands?

Neurological receptors

Signal transduction receptors (correct)

Receptor tyrosine kinases

Structural receptors

Which of the following best describes a receptor agonist?

A substance that enhances receptor activity (correct)

A substance that has no effect on receptors

A substance that inhibits signal transduction

A substance that blocks receptor activity

What roles do scaffold proteins play in signal transduction?

Inhibit receptor activity

Organize signaling complexes (correct)

Transduce signals themselves

Degrade signaling molecules

Which type of substance does NOT act as a ligand?

Receptor Signup and view all the answers

What does the dissociation constant (KD) represent?

The concentration of ligand required to occupy 50% of receptors Signup and view all the answers

What is the primary outcome of ligand-receptor interactions?

Reversible binding Signup and view all the answers

Which factor does NOT directly affect the amount of ligand bound to receptors?

Affinities of other ligands Signup and view all the answers

What technique provides a direct measure of receptor density?

Radioimmunoassay (RIA) Signup and view all the answers

In the context of ligand-receptor interactions, what is better referred to as the affinity constant (KA)?

Rate of ligand binding to receptor Signup and view all the answers

Which type of receptor antagonist competes with the ligand for the same binding site?

Competitive antagonist Signup and view all the answers

What is the primary function of signal transduction in a cell?

Transforming one type of signal into another Signup and view all the answers

What is typically observed during the saturation binding curve?

Binding sites reach a maximal limit at steady state Signup and view all the answers

Which of the following is NOT a typical duration of biological responses in signal transduction?

Weeks for protein folding Signup and view all the answers

Which of the following accurately describes amplification in signal transduction?

Activation of a catalyst resulting in multiple target activations Signup and view all the answers

What effect does adaptation have in a signaling system?

Restores signaling levels to pre-stimulus after stimulation Signup and view all the answers

What is one consequence of defects in signaling pathways?

Development of various diseases Signup and view all the answers

Cross-talk in eukaryotic signal transduction networks primarily provides what benefit?

Enhanced integration of multiple receptor signals Signup and view all the answers

What is a key characteristic of the functional response in signal transduction?

It is achieved once the signal reaches its target Signup and view all the answers

Which statement about receptors in signal transduction is true?

They facilitate the binding of signaling molecules to proteins Signup and view all the answers

What is a key characteristic of the recognition property of receptors?

Receptors should exhibit stereoselectivity. Signup and view all the answers

Which receptor type is associated with tyrosine kinase activity?

Enzyme receptors Signup and view all the answers

What must occur for transduction of a signal to take place?

The receptor must facilitate transmission of the signal into the cell. Signup and view all the answers

Which of the following statements is true regarding the property of saturability in receptors?

Receptors are present in limited amounts. Signup and view all the answers

What is the correct sequence of events in signal transmission after ligand-receptor interaction?

Initiation -> Transmission -> Nuclear or cytoplasmic events -> Biological effects Signup and view all the answers

Which type of receptors directly correlates with G protein-coupled signaling pathways?

Membrane bound receptors Signup and view all the answers

Which statement about reversibility in receptor binding is accurate?

Binding must happen non-covalently through weak forces. Signup and view all the answers

Which receptors are linked to intracellular and nuclear responses?

IP3 receptors and steroid hormone receptors Signup and view all the answers

What does EC50 represent in pharmacology?

The concentration at which a drug exerts 50% of its total activity Signup and view all the answers

Which type of ligand binds reversibly to the same site as the endogenous ligand?

Competitive antagonist Signup and view all the answers

What is the primary effect of a partial agonist when bound to a receptor?

It has weak effects alone but can antagonize the effect of a full agonist Signup and view all the answers

What distinguishes a non-competitive antagonist from a competitive antagonist?

Non-competitive antagonists cannot be overcome by additional agonist Signup and view all the answers

Which ligand type does NOT bind to the active site of a receptor?

Allosteric modulator Signup and view all the answers

What change occurs in the presence of a competitive antagonist on the dose-response curve?

A rightward shift indicating decreased potency without affecting Emax Signup and view all the answers

What is a characteristic effect of irreversible antagonists?

They cause permanent modification of the receptor Signup and view all the answers

Study Notes

BIOC 325: Receptors and Signal Transduction

Course Coordinator: Dr. Ayad Jaffa, DTS 4th floor, email: [email protected]
Teaching Assistant: (information not available)

Resources

Signal transduction (3rd edition), 2015, by IJsbrand M. Kramer, ISBN: 9780123948038, eBook ISBN: 9780123948199
Signal Transduction: Principles, Pathways, and Processes 1st Edition, by Lewis Cantley (Editor), Tony Hunter (Editor), Richard Sever (Editor), Jeremy Thorner (Editor)

BIOC 325 Course: Fall Schedule 2022 (Tentative)

August 30: Topic 1: Signal Transduction: Definition and Pharmacological Introduction
September 4: Topic 2: Roles of Structural Domains and Scaffold Proteins in Signal Transduction
September 6: Topic 3: 7TM G-protein Coupled Receptors, General Features, Effector Systems, and Second Messengers (Part 1): Adenylate Cyclase
September 11: Effector Systems and Second Messengers (Part 2): PLCB
September 13: Calcium in Signaling
September 18: Proteins associated with GPCR (Part 1): GRKs, RGS
September 20: Proteins associated with GPCR (Part 2): β-Arrestin, Dynamin, Clathrin
September 25: GPCR Desensitization, Internalization, and Recycling
September 27: Special GPCRs: Protease-Activated Receptors (PARs) and GPCR Heterodimerization
October 2: Classical methods to assess signaling and coupling of GPCRS
October 4: Topic 4: Receptor Tyrosine Kinase (RTKs) and Important Kinases Downstream of RTKs
October 9: Topic 5: Mitogen-Activated Protein Kinases (MAPKs) and Transactivation of EGFRs by GPCRs
October 11: Topic 6: Nuclear Receptors
October 16, October 18, October 23: Article presentations and discussions
September 28: EXAM 1
October 26: EXAM 2

Student Evaluation

Student Presentation: 15%
Midterm Exam: 35%
Final Exam: 45%
Class Participation: 5%

Lecture 1: Introduction into Signal Transduction

Aims: Define signal transduction, overview steps of signal propagation, receptor types and properties, define receptor agonists and antagonists.

Receptors

Receptors are structural proteins on the surface or inside of a cell that selectively receive and bind a specific substance (ligand) and elicit a specific response.

Types of Receptors

Membrane bound receptors: G Protein coupled receptors, Adrenergic receptors, Angiotensin II, Bradykinin, Enzyme receptors, Tyrosine kinase, Ligand gated ion channel receptors, Nicotinic, GABA, glutamate
Intracellular and nuclear receptors: IP3 receptor (ER), Steroid hormones receptor

G Protein Coupled Receptors (GPCRs)

Enzyme-like Receptors

Ligand-Gated Ion Channel Receptors

Intracellular Receptors

Properties of Receptors

A. Recognition: Saturability, Reversibility, Stereo-selectivity, Agonist specificity, Tissue specificity
B. Transduction: Linking to effector systems (either directly or through intermediate signal amplification systems).

What is Signal Transduction?

The relaying of molecular signals or physical signals from a cell's exterior to its intracellular response mechanisms.

Steps of Cell Signaling

Initiation of signal
Transmission of signal
Nuclear or cytoplasmic events
Biological effects

Steps of Signal Processing

Initiation: interaction of ligand with its receptor
Transmission: receptor transmitting the signal into the cell
Nuclear or cytoplasmic events
Biological effects

Signal Transduction

Involved in multiple biological processes (proliferation, migration, apoptosis)
Defects in signaling pathways can lead to various diseases (cardiovascular, Alzheimer's, cancer)

Signal Transduction Refer to any process by which a cell converts one kind of signal or stimulus into another.

Signal Transduction Cascade

Signal reception
Signal integration
Signal amplification
Signal reaches its target (functional response)

Signal Transduction Cascade: Integration, Amplification, and Adaptation

Integration: Several receptors activate/deactivate the same catalyst. Cross-talk in eukaryotic networks adds another level.
Amplification: Activation of catalysts (e.g., protein kinases) amplifies the input of a single unit into many target molecules.
Adaptation: Return of the signaling system to the pre-stimulus levels while stimulus persists. This allows cells to perceive changes in stimulus size rather than the absolute stimulus level (feedback).

Ligands

Are substances that bind to receptors to trigger a biological activity.
They're signal-triggering molecules binding to a site on a target protein to transfer information
Types: Peptides (short proteins), small molecules (neurotransmitters, hormones, pharmaceutical drugs, toxins), lipids, photons/light particles

Ligand-Receptor Interaction: Law of Mass Action

Ligand-receptor interaction follows simple mass-action relationships.
When a ligand combines with a receptor, it does so at a rate dependent on the concentration of both.
Formulas for rate of association (k₁), rate of dissociation (k₂), Dissociation Constant (KD), and Affinity Constant (KA) are given.
KD represents the ligand concentration required to occupy 50% of receptor binding sites.

Law of Mass Action (Saturation Binding Curve)

Activation of membrane receptors and target cell responses is proportional to the degree of receptor occupancy. KD values indicate affinity of binding. Drug A or B is associated with a particular KD in figures.

Characterizing Receptors and Ligand-Receptor Interactions

Radioimmunoassay (RIA)
Dose-response experiments
Use of receptor antagonists (competitive, non-competitive)

Characterizing Receptors Using Radioimmunoassays (RIA)

Direct measure of receptor number/density and ligand affinity/selectivity utilizing radio-labeled ligands (125I, 35S, or 3H).
Selecting a proper radio-ligand is essential, especially in agonist vs. antagonist contexts. Higher affinity generally favours antagonists.
Saturation binding curves are theoretical (occur during steady state/equilibrium).

Characterizing Receptors Using Radioimmunoassays (RIA): Important Notes

The amount of ligand bound is affected by the number of receptors, ligand concentration, and ligand affinity.

Characterizing Receptors Using Dose-Response Experiments

Measures the functional response of a ligand/drug, which is indirectly assessing receptor binding.
Can be conducted in vitro, in vivo or ex vivo. Graphs shown demonstrating dose-response curves presented in linear and log scale.

Ligands: Agonists, Antagonists, and Partial Agonists

Agonists: Bind to the active site of receptors and lead to a specific effect.
Antagonists: Prevent agonist-mediated responses by obstructing binding and eliminating the normal response.
Partial agonists: Have moderate binding or effect alone, yet exhibit antagonistic effects in the presence of agonists.

Agonists/Antagonists

an agonist drug structure is similar to an endogenous ligand, it so binds to same receptor and produces similar effects shown in figures with agonist/antagonist plots.

Agonists and Partial Agonists

Not all agonists produce the same maximal response at the same receptor. Figure shows comparative graphs of A, B, C which are agonist, with C as partial agonist in figure
The response of the drug (i.e. maximal response) is related to different affinities of the receptors with various agonists as shown by the plots

Receptor Antagonists

Antagonists halt agonist-mediated responses by preventing receptor binding and any typical effect. Two types of antagonists exist.
Competitive: Reversibly binds to the same site as endogenous ligand blocking it. The effect can be overcome by more agonist. There is no change in the maximal response (E_max ) or the affinity but the EC₅₀ (concentrations that produce 50% of its effect) is changed
Non-competitive: Binds to an allosteric site (different binding site to agonist), does not prevent formation of the L–R complex, impairs response triggering, and cannot be reversed. E_max and B_max are reduced and the EC₅₀ values are not affected in figure.

Examples of Agonists and their Receptors

Neurotransmitters, neuropeptides, ions (e.g., Na+, Ca2+)
Hormones (e.g., Growth Hormone)

Second Messengers

Molecules activated after ligand binding (first messenger) to propagate the signal.
Released/activated within a cell to initiate biological processes (proliferation, differentiation, migration, survival, apoptosis).
Examples include cAMP, cGMP, IP3, DAG, and Ca2+.

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Test your knowledge on essential concepts from the chapter covering receptor interactions in biochemistry. This quiz includes questions on GPCRs, ligand-receptor dynamics, and the overall assessment structure of the course. Prepare for a deeper understanding of signal transduction and receptor functionality.