Structural highlights
Function
[CNR1_HUMAN] Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.[1]
Publication Abstract from PubMed
The structure of the C-terminal region of the third cytoplasmic loop (IC3) of the cannabinoid receptor one (CB1) bound to G(alphai1) has been determined using transferred nuclear Overhauser effects (NOEs). The wild-type IC3 sequence is helical when associated with G(alphai1). In contrast, a peptide containing the amino-acid inversion, Ala(341)-Leu(342) adopts a single turn. These findings correlate with the attenuated G(i) association of CB1 with the Ala(341)-Leu(342) mutation previously observed in vivo and the diminished stimulation of G(alphai1) GTPase activity by the corresponding peptide demonstrated in vitro here. These results, the first to report the structure of a GPCR domain while associated with G protein, imply the C-terminus of CB1 IC3, a region with high-sequence conservation among G-protein coupled receptors, must be helical for efficient coupling and activation of the G(i) protein.
Cannabinoid receptor-G protein interactions: G(alphai1)-bound structures of IC3 and a mutant with altered G protein specificity.,Ulfers AL, McMurry JL, Miller A, Wang L, Kendall DA, Mierke DF Protein Sci. 2002 Oct;11(10):2526-31. PMID:12237474[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, Elebring T, Sjogren S, Greasley PJ. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005 Jan 3;579(1):259-64. PMID:15620723 doi:http://dx.doi.org/10.1016/j.febslet.2004.11.085
- ↑ Ulfers AL, McMurry JL, Miller A, Wang L, Kendall DA, Mierke DF. Cannabinoid receptor-G protein interactions: G(alphai1)-bound structures of IC3 and a mutant with altered G protein specificity. Protein Sci. 2002 Oct;11(10):2526-31. PMID:12237474
