7C4S

Sphingosine-1-phosphate receptor 3 with a natural ligand.

7C4S の概要

• エントリーDOI: 10.2210/pdb7c4s/pdb
• 分子名称: Antibody Fab fragment light chain, Antibody Fab fragment heavy chain, Sphingosine 1-phosphate receptor 3, ... (4 entities in total)
• 機能のキーワード: g protein-coupled receptor, signaling protein, agonist, natural ligand, lysophospholipid, regulator of immune system and vascular integrity., membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 179359.97

構造登録者

Iwata, S.,Maeda, S.,Luo, F.,Nango, E.,hirata, K.,Asada, H. (登録日: 2020-05-18, 公開日: 2021-06-09, 最終更新日: 2023-11-29)

主引用文献

Maeda, S.,Shiimura, Y.,Asada, H.,Hirata, K.,Luo, F.,Nango, E.,Tanaka, N.,Toyomoto, M.,Inoue, A.,Aoki, J.,Iwata, S.,Hagiwara, M.
Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias.
Sci Adv, 7:-, 2021

PubMed Abstract: Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the "quartet core") exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein-coupled receptors and will help the design of biased ligands for optimized therapeutics.

PubMed: 34108205
DOI: 10.1126/sciadv.abf5325

実験手法

X-RAY DIFFRACTION (3.2 Å)