Computational prediction of the coupling specificity of G protein-coupled receptors

2007 ◽  
Vol 141 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Zhenran Jiang ◽  
Cuiping Guan ◽  
Yanhong Zhou
2014 ◽  
Vol 10 (11) ◽  
pp. 5149-5160 ◽  
Author(s):  
Supriyo Bhattacharya ◽  
Sangbae Lee ◽  
Reinhard Grisshammer ◽  
Christopher G. Tate ◽  
Nagarajan Vaidehi

2006 ◽  
Vol 65 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Yanzhi Guo ◽  
Menglong Li ◽  
Minchun Lu ◽  
Zhining Wen ◽  
Zhongtian Huang

2007 ◽  
Vol 293 (4) ◽  
pp. E1021-E1029 ◽  
Author(s):  
Shih-Han Hsu ◽  
Ching-Wei Luo

Although only 16 genes have been identified in mammals, several Gα subunits can be simultaneously activated by G protein-coupled receptors (GPCRs) to modulate their complicated functions. Current GPCR assays are limited in the evaluation of selective Gα activation, thus not allowing a comprehensive pathway screening. Because adenylyl cyclases are directly activated by Gsα and the carboxyl termini of the various Gα proteins determine their receptor coupling specificity, we proposed a set of chimeric Gsα where the COOH-terminal five amino acids are replaced by those of other Gα proteins and used these to dissect the potential Gα linked to a given GPCR. Unlike Gqα, G12α, and Giα outputs, compounding the signals from several Gα members, the chimeric Gsα proteins provide a superior molecular approach that reflects the previously uncharacterized pathways of GPCRs under the same cAMP platform. This is, to our knowledge, the first time allowing verification of the whole spectrum of Gα coupling preference of adenosine A1 receptor, reported to couple to multiple G proteins and modulate many physiological processes. Furthermore, we were able to distinguish the uncharacterized pathways between the two neuromedin U receptors (NMURs), which distribute differently but are stimulated by a common agonist. In contrast to the Gq signals mainly conducted by NMUR1, NMUR2 routed preferentially to the Gi pathways. Dissecting the potential Gα coupling to these GPCRs will promote an understanding of their physiological roles and benefit the pharmaceutical development of agonists/antagonists by exploiting the selective affinity toward a certain Gα subclass.


2001 ◽  
Vol 17 (Suppl 1) ◽  
pp. S174-S181 ◽  
Author(s):  
S. Moller ◽  
J. Vilo ◽  
M. D.R. Croning

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