Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition.
Cell Res
; 31(12): 1263-1274, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1414176
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sphingosine-1-Phosphate Receptors
Limits:
Humans
Language:
English
Journal:
Cell Res
Year:
2021
Document Type:
Article
Affiliation country:
S41422-021-00566-x
Similar
MEDLINE
...
LILACS
LIS