7M8W

XFEL crystal structure of the prostaglandin D2 receptor CRTH2 in complex with 15R-methyl-PGD2

7M8W の概要

• エントリーDOI: 10.2210/pdb7m8w/pdb
• 分子名称: Prostaglandin D2 receptor 2, Endolysin chimera, 15R-methyl-prostaglandin D2, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: prostaglandin d2 receptor, crth2, 15r-methyl-pgd2, g protein-coupled receptor, gpcr, endolysin fusion, membrane protein, lcp
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53287.62

構造登録者

Shiriaeva, A.,Han, G.W.,Cherezov, V. (登録日: 2021-03-30, 公開日: 2021-08-25, 最終更新日: 2023-10-18)

主引用文献

Liu, H.,Deepak, R.N.V.K.,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.USA, 118:-, 2021

PubMed Abstract: Prostaglandin D (PGD) 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 PGD derivative, 15R-methyl-PGD (15mPGD), by serial femtosecond crystallography. The structure revealed a "polar group in"-binding mode of 15mPGD contrasting the "polar group out"-binding mode of PGE 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.

PubMed: 34341104
DOI: 10.1073/pnas.2102813118

実験手法

X-RAY DIFFRACTION (2.61 Å)