7EW1

Cryo-EM structure of siponimod -bound Sphingosine-1-phosphate receptor 5 in complex with Gi protein

Summary for 7EW1

• Entry DOI: 10.2210/pdb7ew1/pdb
• EMDB information: 31344
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total)
• Functional Keywords: homo sapiens, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 159201.60

Authors

Yuan, Y.,Jia, G.W.,Shao, Z.H.,Su, Z.M. (deposition date: 2021-05-24, release date: 2021-09-29, Last modification date: 2022-02-16)

Primary citation

Yuan, Y.,Jia, G.,Wu, C.,Wang, W.,Cheng, L.,Li, Q.,Li, Z.,Luo, K.,Yang, S.,Yan, W.,Su, Z.,Shao, Z.
Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition.
Cell Res., 31:1263-1274, 2021

PubMed Abstract: Sphingosine-1-phosphate (S1P) is an important bioactive lipid molecule in cell membrane metabolism and binds to G protein-coupled S1P receptors (S1PRs) to regulate embryonic development, physiological homeostasis, and pathogenic processes in various organs. S1PRs are lipid-sensing receptors and are therapeutic targets for drug development, including potential treatment of COVID-19. Herein, we present five cryo-electron microscopy structures of S1PRs bound to diverse drug agonists and the heterotrimeric Gi protein. Our structural and functional assays demonstrate the different binding modes of chemically distinct agonists of S1PRs, reveal the mechanical switch that activates these receptors, and provide a framework for understanding ligand selectivity and G protein coupling.

PubMed: 34526663
DOI: 10.1038/s41422-021-00566-x

Experimental method

ELECTRON MICROSCOPY (3.4 Å)