| Structural highlights
7m8w is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.61Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
D9IEF7_BPT4 PD2R2_HUMAN Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.[1] [2] [3]
Publication Abstract from PubMed
Prostaglandin D2 (PGD2) signals through the G protein-coupled receptor (GPCR) CRTH2 to mediate various inflammatory responses. CRTH2 is the only member of the prostanoid receptor family that is phylogenetically distant from others, implying a nonconserved mechanism of lipid action on CRTH2. Here, we report a crystal structure of human CRTH2 bound to a PGD2 derivative, 15R-methyl-PGD2 (15mPGD2), by serial femtosecond crystallography. The structure revealed a "polar group in"-binding mode of 15mPGD2 contrasting the "polar group out"-binding mode of PGE2 in its receptor EP3. Structural comparison analysis suggested that these two lipid-binding modes, associated with distinct charge distributions of ligand-binding pockets, may apply to other lipid GPCRs. Molecular dynamics simulations together with mutagenesis studies also identified charged residues at the ligand entry port that function to capture lipid ligands of CRTH2 from the lipid bilayer. Together, our studies suggest critical roles of charge environment in lipid recognition by GPCRs.
Molecular basis for lipid recognition by the prostaglandin D2 receptor CRTH2.,Liu H, Deepak RNVK, Shiriaeva A, Gati C, Batyuk A, Hu H, Weierstall U, Liu W, Wang L, Cherezov V, Fan H, Zhang C Proc Natl Acad Sci U S A. 2021 Aug 10;118(32). pii: 2102813118. doi:, 10.1073/pnas.2102813118. PMID:34341104[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med. 2001 Jan 15;193(2):255-61. PMID:11208866
- ↑ Monneret G, Gravel S, Diamond M, Rokach J, Powell WS. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Blood. 2001 Sep 15;98(6):1942-8. PMID:11535533
- ↑ Xue L, Gyles SL, Barrow A, Pettipher R. Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to prostaglandin D(2). Biochem Pharmacol. 2007 Mar 15;73(6):843-53. doi: 10.1016/j.bcp.2006.11.021. Epub, 2006 Dec 1. PMID:17196174 doi:http://dx.doi.org/10.1016/j.bcp.2006.11.021
- ↑ Liu H, Deepak RNVK, Shiriaeva A, Gati C, Batyuk A, Hu H, Weierstall U, Liu W, Wang L, Cherezov V, Fan H, Zhang C. Molecular basis for lipid recognition by the prostaglandin D(2) receptor CRTH2. Proc Natl Acad Sci U S A. 2021 Aug 10;118(32):e2102813118. PMID:34341104 doi:10.1073/pnas.2102813118
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