5zty
From Proteopedia
Crystal structure of human G protein coupled receptor
Structural highlights
FunctionD9IEF7_BPT4 CNR2_HUMAN Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.[1] [2] [3] [4] Publication Abstract from PubMedThe cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 A resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system. Crystal Structure of the Human Cannabinoid Receptor CB2.,Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ Cell. 2019 Jan 24;176(3):459-467.e13. doi: 10.1016/j.cell.2018.12.011. Epub 2019 , Jan 10. PMID:30639103[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
Categories: Escherichia virus T4 | Homo sapiens | Large Structures | Hua T | Li XT | Liu ZJ | Wu LJ
