G protein trimers are named after their a-subunits, which on the basis of their amino acid similarity and, most importantly by their cellular function, are grouped into four families. These include, Gas and Gai/o, which stimulate and inhibit respectively adenylate cyclase, Gaq/11 which stimulates phospholipase C, and the less characterized Ga12/13 family that activates the Na+/H+ exchanger pathway. The specificity of the interaction of a given GPCR with the pool of available intracellular G-proteins is termed coupling selectivity or specificity. The ability of certain GPCRs to interact with more that one types of G-proteins (i.e. Gas and Gai/o) is known as promiscuous coupling selectivity. GPCRs coupled to members of the Ga12/13 family are all exhibiting promiscuous coupling preferences.
Published in Chapter:
Computational Methods for the Prediction of GPCRs Coupling Selectivity
Nikolaos G. Sgourakis (Rensselaer Polytechnic Institute, USA), Pantelis G. Bagos (University of Central Greece, and University of Athens, Greece), and Stavros J. Hamodrakas (University of Athens, Greece)
Copyright: © 2009
|Pages: 15
DOI: 10.4018/978-1-60566-076-9.ch009
Abstract
GPCRs comprise a wide and diverse class of eukaryotic transmembrane proteins with well-established pharmacological significance. As a consequence of recent genome projects, there is a wealth of information at the sequence level that lacks any functional annotation. These receptors, often quoted as orphan GPCRs, could potentially lead to novel drug targets. However, typical experiments that aim at elucidating their function are hampered by the lack of knowledge on their selective coupling partners at the interior of the cell, the G-proteins. Up-to-date, computational efforts to predict properties of GPCRs have been focused mainly on the ligand-binding specificity, while the aspect of coupling has been less studied. Here, we present the main motivations, drawbacks, and results from the application of bioinformatics techniques to predict the coupling specificity of GPCRs to G-proteins, and discuss the application of the most successful methods in both experimental works that focus on a single receptor and large-scale genome annotation studies.