7vdh

Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state2Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state2

Structural highlights

7vdh is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MRGX2_HUMAN] Mast cell-specific receptor for basic secretagogues, i.e. cationic amphiphilic drugs, as well as endo- or exogenous peptides, consisting of a basic head group and a hydrophobic core (PubMed:25517090). Recognizes and binds small molecules containing a cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal neuromuscular blocking drugs (NMBDs), including tubocurarine and atracurium. In response to these compounds, mediates pseudo-allergic reactions characterized by histamine release, inflammation and airway contraction (By similarity). Acts as a receptor for a number of other ligands, including peptides and alkaloids, such as cortistatin-14, proadrenomedullin N-terminal peptides PAMP-12 and, at lower extent, PAMP-20, antibacterial protein LL-37, PMX-53 peptide, beta-defensins, and complanadine A.[UniProtKB:Q3KNA1]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Kamohara M, Matsuo A, Takasaki J, Kohda M, Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M. Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun. 2005 May 20;330(4):1146-52. doi:, 10.1016/j.bbrc.2005.03.088. PMID:15823563 doi:http://dx.doi.org/10.1016/j.bbrc.2005.03.088
↑ Subramanian H, Kashem SW, Collington SJ, Qu H, Lambris JD, Ali H. PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13. doi: 10.1124/mol.111.071472. Epub 2011 Mar, 11. PMID:21441599 doi:http://dx.doi.org/10.1124/mol.111.071472
↑ Subramanian H, Gupta K, Guo Q, Price R, Ali H. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization. J Biol Chem. 2011 Dec 30;286(52):44739-49. doi: 10.1074/jbc.M111.277152. Epub, 2011 Nov 8. PMID:22069323 doi:http://dx.doi.org/10.1074/jbc.M111.277152
↑ Subramanian H, Gupta K, Lee D, Bayir AK, Ahn H, Ali H. beta-Defensins activate human mast cells via Mas-related gene X2. J Immunol. 2013 Jul 1;191(1):345-52. doi: 10.4049/jimmunol.1300023. Epub 2013 May, 22. PMID:23698749 doi:http://dx.doi.org/10.4049/jimmunol.1300023
↑ Johnson T, Siegel D. Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3512-5. doi: 10.1016/j.bmcl.2014.05.060. , Epub 2014 May 27. PMID:24930830 doi:http://dx.doi.org/10.1016/j.bmcl.2014.05.060
↑ McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, Dong X. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015 Mar 12;519(7542):237-41. doi: 10.1038/nature14022. Epub 2014 Dec 17. PMID:25517090 doi:http://dx.doi.org/10.1038/nature14022
↑ Robas N, Mead E, Fidock M. MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem. 2003 Nov 7;278(45):44400-4. doi: 10.1074/jbc.M302456200. Epub 2003, Aug 12. PMID:12915402 doi:http://dx.doi.org/10.1074/jbc.M302456200

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OCA

[1] Kamohara M, Matsuo A, Takasaki J, Kohda M, Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M. Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun. 2005 May 20;330(4):1146-52. doi:, 10.1016/j.bbrc.2005.03.088. PMID:15823563 doi:http://dx.doi.org/10.1016/j.bbrc.2005.03.088

[2] Subramanian H, Kashem SW, Collington SJ, Qu H, Lambris JD, Ali H. PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13. doi: 10.1124/mol.111.071472. Epub 2011 Mar, 11. PMID:21441599 doi:http://dx.doi.org/10.1124/mol.111.071472

[3] Subramanian H, Gupta K, Guo Q, Price R, Ali H. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization. J Biol Chem. 2011 Dec 30;286(52):44739-49. doi: 10.1074/jbc.M111.277152. Epub, 2011 Nov 8. PMID:22069323 doi:http://dx.doi.org/10.1074/jbc.M111.277152

[4] Subramanian H, Gupta K, Lee D, Bayir AK, Ahn H, Ali H. beta-Defensins activate human mast cells via Mas-related gene X2. J Immunol. 2013 Jul 1;191(1):345-52. doi: 10.4049/jimmunol.1300023. Epub 2013 May, 22. PMID:23698749 doi:http://dx.doi.org/10.4049/jimmunol.1300023

[5] Johnson T, Siegel D. Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3512-5. doi: 10.1016/j.bmcl.2014.05.060. , Epub 2014 May 27. PMID:24930830 doi:http://dx.doi.org/10.1016/j.bmcl.2014.05.060

[6] McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, Dong X. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015 Mar 12;519(7542):237-41. doi: 10.1038/nature14022. Epub 2014 Dec 17. PMID:25517090 doi:http://dx.doi.org/10.1038/nature14022

[7] Robas N, Mead E, Fidock M. MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem. 2003 Nov 7;278(45):44400-4. doi: 10.1074/jbc.M302456200. Epub 2003, Aug 12. PMID:12915402 doi:http://dx.doi.org/10.1074/jbc.M302456200

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