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The cannabinoid type‐1 receptor carboxyl‐terminus, more than just a tail
Author(s) -
Stadel Rebecca,
Ahn Kwang H.,
Kendall Debra A.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07186.x
Subject(s) - g protein coupled receptor , receptor , transmembrane protein , cannabinoid receptor , transmembrane domain , internalization , biology , chemistry , biochemistry , microbiology and biotechnology , antagonist
J. Neurochem. (2011) 117 , 1–18. Abstract The cannabinoid type‐1 (CB 1 ) receptor is a G protein‐coupled receptor that binds the main active ingredient of marijuana, Δ 9 ‐tetrahydrocannabinol, and has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. In the two decades since the discovery of CB 1 , studies at the molecular level have centered on the transmembrane core. This interest has now expanded as we discover that other regions of CB 1 , including the CB 1 carboxyl‐terminus, have critical structures that are important for CB 1 activity and regulation. Following the recent description of the three dimensional structure of the full‐length CB 1 carboxyl‐terminal tail [ Biopolymers (2009) vol. 91, pp. 565–573], several residues and structural motifs including two α‐helices (termed H8 and H9) have been postulated to interact with common G protein‐coupled receptor accessory proteins, such as G‐proteins and β‐arrestins. This discourse will focus on the CB 1 carboxyl‐terminus; our current understanding of the structural features of this region, evidence for its interaction with proteins, and the impact of structure on the binding and regulatory function of CB 1 accessory proteins. The involvement of the carboxyl‐terminus in the receptor life cycle including activation, desensitization, and internalization will be highlighted.