| Structural highlights
Function
C562_ECOLX Electron-transport protein of unknown function.FPR2_HUMAN Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophil chemotactic factors (PubMed:1374236). Binding of FMLP to the receptor causes activation of neutrophils (PubMed:1374236). This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:1374236). The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of proinflammatory signals such as LTB4 (leukotriene B4) (PubMed:9547339). Receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation (By similarity).[UniProtKB:O88536][1] [2]
Publication Abstract from PubMed
The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, and has been considered as a drug target for chronic inflammatory diseases. A variety of peptides with different structures and origins have been characterized as FPR2 ligands. However, the ligand-binding modes of FPR2 remain elusive, thereby limiting the development of potential drugs. Here we report the crystal structure of FPR2 bound to the potent peptide agonist WKYMVm at 2.8 A resolution. The structure adopts an active conformation and exhibits a deep ligand-binding pocket. Combined with mutagenesis, ligand binding and signaling studies, key interactions between the agonist and FPR2 that govern ligand recognition and receptor activation are identified. Furthermore, molecular docking and functional assays reveal key factors that may define binding affinity and agonist potency of formyl peptides. These findings deepen our understanding about ligand recognition and selectivity mechanisms of the formyl peptide receptor family.
Structural basis of ligand binding modes at the human formyl peptide receptor 2.,Chen T, Xiong M, Zong X, Ge Y, Zhang H, Wang M, Won Han G, Yi C, Ma L, Ye RD, Xu Y, Zhao Q, Wu B Nat Commun. 2020 Mar 5;11(1):1208. doi: 10.1038/s41467-020-15009-1. PMID:32139677[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ye RD, Cavanagh SL, Quehenberger O, Prossnitz ER, Cochrane CG. Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor. Biochem Biophys Res Commun. 1992 Apr 30;184(2):582-9. doi:, 10.1016/0006-291x(92)90629-y. PMID:1374236 doi:http://dx.doi.org/10.1016/0006-291x(92)90629-y
- ↑ Gronert K, Gewirtz A, Madara JL, Serhan CN. Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release. J Exp Med. 1998 Apr 20;187(8):1285-94. doi: 10.1084/jem.187.8.1285. PMID:9547339 doi:http://dx.doi.org/10.1084/jem.187.8.1285
- ↑ Chen T, Xiong M, Zong X, Ge Y, Zhang H, Wang M, Won Han G, Yi C, Ma L, Ye RD, Xu Y, Zhao Q, Wu B. Structural basis of ligand binding modes at the human formyl peptide receptor 2. Nat Commun. 2020 Mar 5;11(1):1208. doi: 10.1038/s41467-020-15009-1. PMID:32139677 doi:http://dx.doi.org/10.1038/s41467-020-15009-1
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