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Cannabinoid Receptor-G Protein Interactions: Gαi1-Bound Structures of IC3 and a Mutant with Altered G Protein Specificity
Protein Science (2002)
  • Amy L. Ulfers, Brown University
  • Jonathan L. McMurry, Kennesaw State University
  • Alexander Miller, University of Connecticut - Storrs
  • Ligong Wang, University of Connecticut - Storrs
  • Debra A. Kendall, University of Connecticut - Storrs
  • Dale F. Mierke, Brown University
Abstract

The structure of the C-terminal region of the third cytoplasmic loop (IC3) of the cannabinoid receptor one (CB1) bound to Gαi1 has been determined using transferred nuclear Overhauser effects (NOEs). The wild-type IC3 sequence is helical when associated with Gαi1. In contrast, a peptide containing the amino-acid inversion, Ala341-Leu342 adopts a single turn. These findings correlate with the attenuated Gi association of CB1 with the Ala341-Leu342 mutation previously observed in vivo and the diminished stimulation of Gαi1 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 Gi protein.

Disciplines
Publication Date
October, 2002
Citation Information
Amy L. Ulfers, Jonathan L. McMurry, Alexander Miller, Ligong Wang, et al.. "Cannabinoid Receptor-G Protein Interactions: Gαi1-Bound Structures of IC3 and a Mutant with Altered G Protein Specificity" Protein Science Vol. 11 Iss. 10 (2002)
Available at: http://works.bepress.com/jonathan_mcmurry/11/