GPCR Oligomerization Overview

When two different receptor proteins join together to form a functional unit.

Drugs designed to bind to two different receptors simultaneously, often promoting heterodimerization.

Drugs formed by linking two single molecule drugs (monovalent ligands) to target receptors.

Drugs that specifically target only the heterodimer form of two receptors, avoiding interaction with the individual receptors.

A drug designed to fit a unique binding site that only exists when two receptors are heterodimerized.

The process where G-protein coupled receptors (GPCRs) form complexes with other GPCRs, typically as dimers (two units).

An oligomeric complex formed by two identical GPCR subunits.

An oligomeric complex formed by two different GPCR subunits.

Heterodimers can exhibit unique signaling properties compared to their individual subunits.

Heterodimers can bind to ligands that only bind to the complex, not the individual subunits.

Dimerization can be essential for the proper folding and trafficking of GPCRs from the ER to the cell surface.

Ligand binding can influence GPCR dimerization, either promoting or inhibiting its formation.

Oligomerization can impact how GPCRs move within the cell, affecting their distribution and function.

The formation of a dimer (two receptors bound together) that is triggered by the presence of a ligand (a molecule that binds to a receptor).

The formation of a dimer (two receptors bound together) that occurs independently of ligand binding.

When the binding of one ligand to a receptor in a heterodimer increases the affinity (attraction) of the other receptor for its ligand.

When the binding of one ligand to a receptor in a heterodimer decreases the affinity (attraction) of the other receptor for its ligand.

The specific type of G protein that a receptor can interact with. Heterodimerization can alter this.

The process of two receptors being taken into the cell together after only one receptor is activated by a ligand. This is often seen with heterodimers.

A model of GPCR dimerization in which receptors interact via their transmembrane domains, but their overall monomeric structures remain intact.

A model of GPCR dimerization in which segments of the transmembrane domains are swapped between two receptors, leading to a more intertwined structure.

A technique that uses agents to link proteins together, forming larger complexes. These complexes can be detected using Western blotting, revealing the presence of receptor interactions.

A method used to identify protein-protein interactions. Antibodies specific to a target protein are used to capture interacting proteins, forming a complex that can be analyzed to identify binding partners and their characteristics.

A biophysical technique that uses fluorescent molecules (donor and acceptor) to measure the distance between them. When the donor is excited, it can transfer energy to the acceptor if they are close enough, resulting in fluorescence emission by the acceptor.

Similar to FRET, but uses a bioluminescent donor molecule instead of a fluorescent one. It is used to study protein interactions in living cells, providing information on their proximity and interaction dynamics.

A technique that uses mass spectrometry to analyze the molecular weights of proteins. It can be used to determine the composition and stoichiometry (the relative amounts of each component) of protein complexes, like GPCRs and G proteins.

Förster Resonance Energy Transfer is a process where energy is transferred non-radiatively from an excited donor fluorophore to an acceptor fluorophore, resulting in the acceptor fluorophore's emission.

The distance over which FRET can occur is limited to approximately 4-10 nanometers.

Efficient FRET requires significant spectral overlap between the donor's emission spectrum and the acceptor's absorption spectrum.

FRET can be used to detect the binding of a substrate-sensory protein domain, which induces a conformation change and results in FRET.

FRET can detect ligand-receptor binding, where the binding event causes a conformational change leading to FRET.

FRET can be used in systems with two fluorophores attached to a complex unit. Upon stimulation, the complex undergoes a conformational change leading to FRET.

FRET can be used to detect proteolytic cleavage events. When cleavage happens, the fluorophores are separated, and FRET is lost.

Bioluminescence Resonance Energy Transfer (BRET) involves energy transfer from a bioluminescent donor to a fluorescent acceptor. It utilizes luciferase, a bioluminescent enzyme, as the donor.

The process of forming heterodimers can modify the biochemical, pharmacological, and functional characteristics of receptors.

Laboratory-based experiments investigating GPCR signaling and coupling using different approaches to analyze receptor function.

Cells modified to express specific genes, often used for studying drug-receptor interactions and signal transduction.

Determining how well a GPCR is working by analyzing its interaction with drugs (ligands) and its downstream signaling pathways.

Measuring the formation of GPCR heterodimers using techniques like FRET and BRET, which detect interactions between different proteins.

Analyzing how GPCRs move inside a cell, particularly during receptor activation and signaling.

Different types of molecules (ligands) used to interact with GPCRs: agonists activate, antagonists block, biased agonists activate specific pathways, bivalent ligands target heterodimers, and allosteric modulators influence receptor behavior.