mProX™ Human MRGPRX1 Stable Cell Line
- Product Category:
- Membrane Protein Stable Cell Lines
- Subcategory:
- GPCR Cell Lines
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Published Data
Fig.1 Der p1 induces IL-6 expression in A549 pulmonary epithelial cells, partially reliant on MRGPRX1.
Knockdown of Mrgprx1 and Par2 alters Il-6 induction by Der p1 in A549 cells. *, p ≤ 0.05; ***, p ≤ 0.005. P values exceeding 0.05 are deemed nonsignificant (Ns).
Ref: Reddy, Vemuri B., and Ethan A. Lerner. "Activation of mas-related G-protein-coupled receptors by the house dust mite cysteine protease Der p1 provides a new mechanism linking allergy and inflammation." Journal of Biological Chemistry 292.42 (2017): 17399-17406.
Pubmed: 28768771
DOI: 10.1074/jbc.M117.787887
Research Highlights
Guo L, et al. "Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.." Nature communications, 2023.
The receptor MRGPRX1, belonging to the Mas-related G protein-coupled receptor family, plays a crucial role in both itch perception and potential treatment of chronic itch and pain. Recent cryo-EM studies reveal the complex structures of MRGPRX1 in its trimeric form when bound to two different peptide ligands, BAM8-22 and CNF-Tx2. These structures demonstrate a flexible and shallow binding pocket that allows for recognition of multiple peptide allergens. Unlike MRGPRX2, MRGPRX1 contains a unique feature that accommodates the "RF/RY" motif of the allergen at the extracellular ends of two transmembrane helices. Furthermore, the crucial involvement of a specific motif inside the ligand binding pocket and on the cytoplasmic side for both the Gi and Gq signaling pathways is also revealed. Overall, these findings provide significant insights into the molecular mechanisms underlying itch sensation, MRGPRX1 activation, and downstream G protein signaling.
Pubmed:
37591889
DOI:
10.1038/s41467-023-40705-z
Gan B, et al. "Mechanism of agonist-induced activation of the human itch receptor MRGPRX1.." PLoS biology, 2023.
The four primate-specific receptors known as Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) have been recently linked to various biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first human MRGPR to be identified and is primarily expressed in sensory neurons. Its dual function in itch and pain signaling pathways has made it a promising target for managing itch and pain. A cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 has been determined. This new compound has shown high potency and selectivity for MRGPRX1, making it a potential pain reliever. MRGPRX1 shares similar structural features with other MRGPRX family members in terms of Gq-mediated receptor activation, but has distinct variabilities in the orthosteric pocket that allow for specific agonist recognition. Combined with receptor activation and itch behavior evaluation assays, this study offers valuable insights for the development of targeted therapies for itch and pain through MRGPRX1 modulation.
Pubmed:
37347749
DOI:
10.1371/journal.pbio.3001975
