Structural highlights
Function
GBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.[1]
Publication Abstract from PubMed
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.
Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition.,Yuan Y, Jia G, Wu C, Wang W, Cheng L, Li Q, Li Z, Luo K, Yang S, Yan W, Su Z, Shao Z Cell Res. 2021 Dec;31(12):1263-1274. doi: 10.1038/s41422-021-00566-x. Epub 2021 , Sep 15. PMID:34526663[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Johnston CA, Kimple AJ, Giguere PM, Siderovski DP. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. PMID:18611381 doi:http://dx.doi.org/10.1016/j.str.2008.04.010
- ↑ 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. 2021 Dec;31(12):1263-1274. PMID:34526663 doi:10.1038/s41422-021-00566-x
