Understanding G-Protein Coupled Receptors Mechanisms

Apr 30, 2024

Mindmap

Lecture Summary: G-Protein Coupled Receptors (GPCRs)

Overview of GPCRs

  • GPCRs are only found in eukaryotes and constitute the largest class of membrane receptors.
  • Humans have over 1,000 types of GPCRs, each with specific functions.
  • They are involved in key body processes such as immune regulation, sensory perceptions, and mood regulation.
  • 30-50% of all modern medicinal drugs target GPCRs.
  • GPCRs interact with a variety of ligands like hormones, neurotransmitters, light-sensitive compounds, and more.

Structure of GPCRs

  • Characterized by seven transmembrane alpha helices.
  • Known as "7-transmembrane receptors" due to their structure.

G-Proteins Structure

  • G-proteins are crucial for GPCR function, enabling them to bind GDP and GTP (guanosine diphosphate and guanosine triphosphate).
  • GPCRs are primarily associated with heterotrimeric G-proteins, which consist of alpha, beta, and gamma subunits.
  • Alpha and gamma subunits are attached to the cell membrane through lipid anchors.

GPCR Signaling Mechanism

Activation and Function

  1. Ligand Binds to GPCR: A specific molecule binds to the GPCR causing a conformational change.
  2. GPCR Undergoes Conformational Change: This change is critical for activating the G-protein.
  3. Alpha Subunit GDP-GTP Exchange: The GPCR-induced change causes the alpha subunit to exchange GDP for GTP.
  4. Dissociation of Alpha Subunit: Post-GTP binding, the alpha subunit dissociates from the beta and gamma subunits.
  5. Alpha Subunit Activates Target Proteins: This can regulate functions of other proteins, stimulate enzyme activity, or open ion channels.
  6. GTP Hydrolyzed to GDP: This step turns off the signal, returning GPCR and G-proteins to their preactivation state.

Example of GPCR Function: Adrenergic Receptor

  • Epinephrine Binding: Triggers conformational change in the GPCR.
  • Activation of Adenylate Cyclase by GTP-bound Alpha: This converts ATP to cyclic AMP (cAMP), a second messenger.
  • Biological Effects: Increases heart rate, dilates blood vessels in muscles, and breaks down glycogen to glucose.

Conclusion

  • GPCRs relay external signals into cellular actions through a complex yet highly regulated process.
  • They play a vital role in numerous physiological responses and adaptations.

This detailed mechanism not only illustrates the fundamental operations of GPCRs but also highlights their medical relevance, especially in drug targeting.