L6 Receptors as drug targets 3

Questions and Answers

What is the primary mechanism through which intrinsic enzyme receptors activate a signal transduction cascade?

Phosphorylation through dimerization and autophosphorylation.

Identify the first step in the activation of intrinsic enzyme receptors.

Ligand binding.

What structural feature characterizes DNA binding receptors, facilitating their role in gene activation?

Zinc fingers.

Name two types of hormones that DNA binding receptors are activated by.

Steroid hormones and thyroid hormones. Signup and view all the answers

Describe the relationship between dimerization and the functionality of intrinsic enzyme receptors.

Dimerization is essential for the formation of a functional receptor, enabling signaling. Signup and view all the answers

What is the final step in the activation process of intrinsic enzyme receptors after autophosphorylation?

Substrate phosphorylation. Signup and view all the answers

To what cellular location do DNA binding receptors translocate after activation in the cytosol?

The nucleus. Signup and view all the answers

List one function of intrinsic enzyme receptors in cellular signaling.

Regulating cellular responses to growth factors and hormones. Signup and view all the answers

Which family of receptors has the largest number of types?

GPCRs have the largest number of types. Signup and view all the answers

Define an orphan receptor.

An orphan receptor is a receptor with a known structure that does not have a known ligand. Signup and view all the answers

What is the next step in the activation of Intrinsic Enzyme Receptors after ligand binding?

Following ligand binding, intrinsic enzyme receptors dimerise. Signup and view all the answers

What is a key requirement for the ligands of DNA Binding Receptors?

Ligands of DNA binding receptors must be lipophilic to cross the plasma membrane. Signup and view all the answers

Compare the amplification levels of ion channel receptors and intrinsic enzyme receptors.

Ion channel receptors have low amplification, while intrinsic enzyme receptors have high amplification. Signup and view all the answers

Why do steroid hormones require dimerization of receptors in the cytosol?

Dimerization is necessary for the receptors to translocate into the nucleus and bind to DNA. Signup and view all the answers

What distinguishes the speed of response between ion channel receptors and DNA binding receptors?

Ion channel receptors have very fast responses, while DNA binding receptors have very slow responses. Signup and view all the answers

Explain the significance of the zinc finger domain in receptor function.

The zinc finger domain binds to DNA to alter gene transcription. Signup and view all the answers

Why has the classification of receptors by ligands become inadequate?

Receptors can be activated by multiple ligands and may respond to more than one ligand. Signup and view all the answers

What are the four families of receptors identified in the context?

The four families are ion channels, GPCRs, intrinsic enzyme receptors, and DNA binding receptors. Signup and view all the answers

What are the three subfamilies of ion channel receptors?

The subfamilies are pentameric, tetrameric, and trimeric. Signup and view all the answers

What structural commonality is shared by all ion channel receptors?

All ion channel receptors share alpha helices in their structure. Signup and view all the answers

What characterizes G-protein coupled receptors (GPCRs) in terms of their membrane structure?

GPCRs are characterized as having seven membrane-spanning domains. Signup and view all the answers

How many genes in the human genome are estimated to code for GPCRs?

Approximately 1200 genes, accounting for about 3-4% of the human genome. Signup and view all the answers

What distinguishes Class A GPCRs from Class B GPCRs regarding their ligand binding site?

Class A GPCRs have their ligand binding site in the transmembrane domain, while Class B GPCRs have it externally. Signup and view all the answers

In Class C GPCRs, where is the ligand binding site located?

The ligand binding site is located in the extracellular domain, and they typically act as dimers. Signup and view all the answers

What are the endogenous ligands for Thyroid Hormone Receptors and Liver X Receptors?

Thyroid Hormone Receptors bind to thyroxine hormones, while Liver X Receptors bind to oxysterols. Signup and view all the answers

Identify the endogenous ligands associated with Glucocorticoid Receptors.

Glucocorticoid Receptors are associated with glucocorticoids. Signup and view all the answers

List all members of subgroup III and their corresponding ligands.

Members include Glucocorticoid Rs (glucocorticoids), Androgen Rs (dihydrotestosterone), Progesterone Rs (progesterone), Estrogen Rs (estrogens), and Estrogen Receptor-Related Rs (orphan). Signup and view all the answers

What ligands do members of subgroup IV bind to?

Members of subgroup IV bind to unsaturated fatty acids and include Nerve Growth Factor IB and Nurr-Related Factor 1. Signup and view all the answers

What function does dimerization serve in the DNA binding receptor activation process?

Dimerization is essential for the formation of a functional receptor complex that can bind DNA. Signup and view all the answers

Which subgroup includes the Chicken Ovalbumin Upstream Promoter Transcription Factors and what type of ligands do they correspond to?

Chicken Ovalbumin Upstream Promoter Transcription Factors are part of subgroup II, and they correspond to orphan ligands. Signup and view all the answers

What is unique about the Germ Cell Nuclear Factor in terms of endogenous ligands?

The Germ Cell Nuclear Factor belongs to subgroup VI and has no known endogenous ligands, categorized as orphan. Signup and view all the answers

Explain the role of translocation in the activation of DNA binding receptors.

Translocation involves the movement of the receptor-ligand complex into the nucleus, crucial for influencing gene transcription. Signup and view all the answers

How are ion channel receptors commonly classified based on their structure?

Ion channel receptors are classified as pentameric, tetrameric, or trimeric depending on the number of subunits. Signup and view all the answers

What types of ions do cationic ion channels typically allow to pass through?

Cationic ion channels typically allow Na+, K+, and Ca2+ ions to pass through. Signup and view all the answers

What distinguishes G-protein coupled receptor subfamilies from each other?

G-protein coupled receptor subfamilies are distinguished by their structural features, such as Class A, B, and C classifications. Signup and view all the answers

Why are intrinsic enzyme receptors significant in pharmacology?

Intrinsic enzyme receptors are significant because they directly activate enzyme activity upon ligand binding, affecting various signaling pathways. Signup and view all the answers

What role do DNA binding receptors play in cellular function?

DNA binding receptors interact with DNA to regulate gene expression, influencing cellular behavior and responses. Signup and view all the answers

Describe how pentameric ion channels differ from tetrameric ion channels in structure.

Pentameric ion channels consist of five subunits, while tetrameric ion channels are made up of four subunits. Signup and view all the answers

What is the significance of the ligand binding site in ion channel receptors?

The ligand binding site is critical for the activation of the channel, as it is where the specific ligand binds to induce conformational changes. Signup and view all the answers

How do receptor operated ion channels facilitate neuronal signaling?

Receptor operated ion channels facilitate neuronal signaling by allowing the influx of ions, which leads to membrane depolarization and action potential generation. Signup and view all the answers

What defines the excitatory nature of certain ion channels in neurotransmission?

The excitatory nature of ion channels, such as those allowing Na+ influx, is defined by their ability to depolarize the neuron and promote action potentials. Signup and view all the answers

In what way do subunit compositions in homopentameric vs heteropentameric channels affect their function?

Homopentameric channels consist of identical subunits, while heteropentameric channels have different subunits, influencing their pharmacological properties and ion selectivity. Signup and view all the answers

Study Notes

Learning Outcomes

Classification of receptors by structure and function.
Recognition of subfamilies within receptor families.
Description of receptor structures in four main families.
Understanding functions of receptors across the four families.

Overview of Receptor Classification

Receptors can be categorized by:
- Function: Opening ion channels, activating G-proteins, triggering enzymes, interacting with DNA.
- Structure: Understanding protein composition and amino acid/nucleotide sequences.

Receptor Families

Major families include:
- Ion channel receptors
- G-protein coupled receptors (GPCRs)
- Intrinsic enzyme receptors
- DNA binding receptors

Ion Channel Receptors

Also known as ionotropic, ligand-gated, or receptor-operated ion channels.
Types include:
- Pentameric (e.g., GABAA, Nicotinic acetylcholine, 5-HT3)
- Tetrameric (e.g., NMDA, AMPA, Kainate receptors)
- Trimeric (e.g., P2X receptors)

Pentameric Ion Channels

Pentameric ion channels are complexes formed by five subunits. These can either be homopentamers, which consist of identical subunits, or heteropentamers, composed of different types of subunits. This structural diversity allows for varying functional properties and regulatory mechanisms.
Ligand binding for pentameric channels occurs in the extracellular space, which is crucial for channel activation. The binding of specific ligands triggers conformational changes that lead to ion flow through the channel.
These channels allow the passage of several common ions: sodium ions (Na⁺) and calcium ions (Ca²⁺) contribute to depolarization of the membrane, while potassium ions (K⁺) and chloride ions (Cl⁻) primarily cause hyperpolarization, which is essential for returning the membrane potential to a resting state.

Tetrameric Ion Channels

Tetrameric ion channels are made up of four subunits, which are always heteropentamers, meaning they are composed of different subunit types. This arrangement is critical for their functioning and specificity to certain ions.
These channels consist of three transmembrane domains that encircle a central flexible pore. The design of the pore adapts according to ion type, ensuring proper ion selectivity and conductance.
They are permeable to common ions such as sodium (Na⁺), potassium (K⁺), and sometimes calcium (Ca²⁺), contributing to various physiological processes, including muscle contraction and neurotransmission.

Trimeric Ion Channels

Trimeric ion channels are organized into three subunits, and their structure prominently features two alpha helices, which play a crucial role in the stability and functionality of the channel.
The architecture of these channels is primarily extracellular, which facilitates the process of depolarization as ions flow through the channel upon activation, playing key roles in signal transduction across neuronal and muscle membranes.

G-Protein Coupled Receptors (GPCRs)

Also referred to as metabotropic, seven membrane-spanning, or serpentine receptors.
Made up of approximately 1200 genes (3-4% of the human genome), with 67% being odorant receptors.
Classes include:
- Class A: Ligand binding site is in the transmembrane domain.
- Class B: Ligand binding occurs externally, suited for large proteins.
- Class C: Bind ligands in the extracellular domain and typically act as dimers.

Intrinsic Enzyme Receptors

Known as pleiotropic or catalytic receptors.
Include receptors for growth factors, cytokines, and insulin.
Function via phosphorylation:
- Steps: Ligand binding, dimerization, autophosphorylation, substrate phosphorylation.

DNA Binding Receptors

Referenced as nuclear receptors or ligand-activated transcription factors, utilizing zinc fingers.
Bind to steroid hormones, thyroid hormones, and retinoic acid.
Activated in the cytosol and migrate to the nucleus to affect transcription.

Properties of Different Receptor Families

Ion Channels: Multiple subunits, very fast response (µs-ms), low amplification.
GPCRs: Single protein, fast response (ms-s), very high amplification.
Intrinsic Enzymes: Often dimers, slow response (mins-hours), high amplification.
DNA Binding: Dimers, very slow response (hours-days), high amplification.

Key Concepts and Terminology

Orphan receptor: A receptor with a known structure but no identified ligand.
Ligands for DNA binding receptors must be lipophilic to cross the plasma membrane.
Receptor types and their mechanisms enable diverse physiological responses and signal amplification.

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Description

This quiz focuses on the classification of receptors as drug targets, emphasizing their structure and function. It will explore various receptor families and subfamilies, enhancing your understanding of pharmacological principles in drug design and development.