6kpc
From Proteopedia
Crystal structure of an agonist bound GPCR
Structural highlights
FunctionENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1] 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.[2] [3] [4] [5] Publication Abstract from PubMedHuman endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1. Here, we report the cryoelectron microscopy structures of synthetic cannabinoid-bound CB2 and CB1 in complex with Gi, as well as agonist-bound CB2 crystal structure. Of important scientific and therapeutic benefit, our results reveal a diverse activation and signaling mechanism, the structural basis of CB2-selective agonists design, and the unexpected interaction of cholesterol with CB1, suggestive of its endogenous allosteric modulating role. Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures.,Hua T, Li X, Wu L, Iliopoulos-Tsoutsouvas C, Wang Y, Wu M, Shen L, Johnston CA, Nikas SP, Song F, Song X, Yuan S, Sun Q, Wu Y, Jiang S, Grim TW, Benchama O, Stahl EL, Zvonok N, Zhao S, Bohn LM, Makriyannis A, Liu ZJ Cell. 2020 Jan 28. pii: S0092-8674(20)30055-6. doi: 10.1016/j.cell.2020.01.008. PMID:32004463[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Enterobacteria phage RB59 | Homo sapiens | Large Structures | Hua T | Li XT | Liu ZJ | Makriyannis A | Wu LJ | Wu M
