PCOL 2-2 ~ 3-1 G Protein-Coupled Receptor

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Questions and Answers

Which of the following is true about GPCR proteins?

They are mainly responsible for taste perception

They have 7 transmembrane domains (TMDs) (correct)

They are involved in more than 70% of drugs

They have 4% of the human genome

What is the approximate number of GPCR family in humans?

1200

400

800 (correct)

100

Which of the following is NOT a role of GPCR proteins?

Sensing light

Sensing odors

Sensing taste

Sensing touch (correct)

What are some examples of ligands that can bind to GPCR proteins?

Lipids Signup and view all the answers

Which of the following cannot be a research technique used to study GPCR proteins?

First messenger neurochemistry Signup and view all the answers

Which of the following is incorrectly matched?

Rhodopsin - Venus flytrap domain Signup and view all the answers

Which receptor class has a hormone receptor motif domain?

Secretin Signup and view all the answers

Which technique was used to develop understanding of structure and receptor activation in proteins?

X-ray crystallography Signup and view all the answers

Why is it more difficult to crystallize proteins in the active state with an agonist bound?

Agonist binding causes a conformational shift Signup and view all the answers

What happens to the α-subunit's affinity for GDP and GTP upon ligand binding?

Affinity for GDP decreases, affinity for GTP increases Signup and view all the answers

Which of the following is incorrect about G-Protein α Subunit Families?

Inhibitory - increases cAMP formation, activate or inhibit ion channels Signup and view all the answers

Which of the following is NOT a function of the G-protein βγ subunit in signaling?

Activating PI3 kinase Signup and view all the answers

Which GPCR receptor class is primarily involved in inhibiting action potential activity through the activation of GIRK K+ channels?

Gi Coupled GPCRs Signup and view all the answers

Which of the following is a major transducer of Gi Coupled GPCRs?

GIRKs Signup and view all the answers

What is the role of the βγ subunits in Gi Coupled G-protein signaling?

Inhibiting action potential via GIRK Signup and view all the answers

Which of the following is true about GPCR modulation compared to ionotropic receptors?

GPCR modulation is slower than ionotropic receptors Signup and view all the answers

Which of the following is NOT a factor affecting the time of action in GPCR signaling?

Ligand concentration Signup and view all the answers

Which drug has the highest intrinsic efficacy among the given options?

Methadone Signup and view all the answers

What is the formula for signal amplification in GPCR signaling?

S = ε[A.R] Signup and view all the answers

Which enzyme phosphorylates the GPCR once the βγ subunits have dissociated?

GRK Signup and view all the answers

What happens to the GPCR once it is phosphorylated by GRK?

It becomes a substrate for β-arrestin Signup and view all the answers

Where does β-arrestin drag the phosphorylated GPCR?

Clathrin-coated pits Signup and view all the answers

What happens to the GPCR once it is in the clathrin-coated pits?

It becomes a vesicle that is sent to the endosome Signup and view all the answers

What are the possible fates of the GPCR in the endosome?

It may eventually return to the membrane, be hydrolysed, or may signal again from the endosome Signup and view all the answers

What is the purpose of the intrinsic feedback process in GPCR regulation?

To lead to desensitization and tolerance Signup and view all the answers

What is an example of GPCRs with highly conserved structures but vastly different physiological effects?

Adrenoreceptors Signup and view all the answers

Which of the following is correctly matched?

Oxycodone - Moderate G-Protein Signal, Weak Arrestin Signal Signup and view all the answers

What is the potential advantage of allosteric binding sites in terms of drug development?

Greater potential for selective drugs Signup and view all the answers

What is the function of DREADDs?

Do not respond to muscarinic receptor agonists Signup and view all the answers

Which GPCR is an algal motility photoreceptor cation conducting protein?

Channelrhodopsin (ChR2) Signup and view all the answers

What is a way GPCR selectivity could be developed?

Receptor number and intrinsic efficacy of agonist Signup and view all the answers

What is the function of Halorhodopsin (ChR2)?

Anion conducting Signup and view all the answers

What are some factors affecting GPCR signaling?

Receptor number and downstream amplification Signup and view all the answers

Study Notes

GPCR Overview

G-Protein Coupled Receptors (GPCRs) are integral membrane proteins involved in various cellular functions.
Humans possess approximately 800 GPCR family members, responsible for diverse physiological actions.

Functions and Roles

GPCRs play critical roles in signal transduction across cell membranes.
Common ligands for GPCRs include hormones, neurotransmitters, and sensory stimuli.
GPCRs participate in pathways influencing mood, vision, taste, and immune functions.

Research and Techniques

Various techniques are utilized in GPCR research, including ligand binding assays and structure–activity relationship studies.
Crystallizing GPCRs in the active state is challenging due to conformational flexibility when an agonist is bound.

G-Protein Dynamics

Upon ligand binding, the α-subunit of the G-protein transitions from a high affinity for GDP to a high affinity for GTP.
The βγ subunit of Gi coupled GPCRs inhibits cellular activity via GIRK (G-protein inwardly-rectifying potassium) channels.
DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) are engineered GPCRs utilized for specific cellular manipulation.

GPCR Signaling and Modulation

Signal amplification in GPCR signaling is often described by the formula 1 receptor → multiple G proteins → extensive downstream signaling.
GPCR phosphorylation by G-Protein Receptor Kinases (GRKs) leads to receptor desensitization.

Internalization and Regulation

Following phosphorylation by GRK, GPCRs are bound by β-arrestin, initiating internalization via clathrin-coated pits.
In the endosome, GPCRs may be recycled back to the surface, targeted for degradation, or undergo translocation to different cellular compartments.

Structural Considerations

Certain GPCRs exhibit conserved structures while producing diverse physiological effects, demonstrating functional plasticity.
Allosteric binding sites on GPCRs allow additional avenues for drug development, enhancing specificity and reducing side effects.

Drug Efficacy and Research Advances

The most efficacious drugs among GPCR targets possess high intrinsic efficacy.
Understanding receptor structure and activation is facilitated by advanced techniques, including X-ray crystallography and cryo-electron microscopy.

Challenges in GPCR Pharmacology

Identifying factors impacting GPCR signaling, such as ligand concentration, receptor density, and the presence of accessory proteins, is vital for therapeutic development.
Researchers aim to enhance GPCR selectivity in drug design to minimize unintended actions and increase treatment effectiveness.

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Description

Test your knowledge on GPCRs, a large and diverse family of proteins with crucial roles in sensing extracellular signals. Learn about their structure, function, and significance as major drug targets. Discover how GPCRs play a role in sensory perception, neurotransmission, hormone regulation, and growth factors.