MRGPRX2 is a certain type of GPCR that is located in the cellular membranes of mast cells.

Background

GCPR’s or G-Protein Coupled Receptors are a special type of protein receptor that promotes cellular signaling. Due to its structure spanning the cellular membrane, it works to transmit extracellular signals to create a change inside the cell. This is called signal transduction, and is a common way extracellular signals produce a change within cells. Some common cellular pathways that utilize GPCR’s are found in Rhodopsin, a protein essential for the human vision response, or the adrenaline fight-or-flight response. Understanding GPCR’s and how they produce their desired intracellular signal is essential understanding essential cellular pathways, especially in their diseased states. As of 2017, there were about 475 drugs in circulation that acted on 108 GPCR targets, and at least 321 GPCR-targeting drugs were in clinical trial stages, with about 20% of them targeting novel GPCR’s. ^[1] Because of the clinical relevance of GPCR’s, every new structure found, such as MRGPRX2, contributes to essential drug development to both treat disease, or modulate harmful side effects.

Because of how many different types of GPCR’s there are, they have been categorized into 6 different classes based on shared sequences and functions.^[2] MRGPRX2 is categorized into the Class A receptor family, however it has important differences that make it a unique type of Class A receptor.

GPCR Structure

Because MRXGPR2 is a standard G-protein from the A family, it shares the same general structural domains of all GPCR's. This includes a and a domain. The G-protein domain consists of , , and subunits.

Transmembrane Domain

G-Protein

Novel Characteristics

The most important findings about the MRGPRX2 receptor are the differences between it and all other previously discovered GPCR's found in the A family. Many conserved structural motifs, characteristic of the A family receptors, are absent on MRGPRX2, which contribute significantly to the different ligand interactions it has.

Toggle Switch

Previously known Tryptophan residue that acts as the Toggle Switch in GPCR is switched to a .

Sodium Site

PIF/LLF Motif

LLF Motif on .

DRY/ ERC Motif

Disulfide Bonds

Disulfide bond connecting .

Ligands

C48/80 ligand description

Function

Before Activation

After Activation

Clinical Relevance

3D Structures

</Structure Section>

References

1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Hauser
2. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Basith

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