Bioinformatics Vol. 17 no. 90001 2001
Pages S174-S181
© 2001 Oxford University Press
Prediction of the coupling specificity of G protein coupled receptors to their G proteins
1 EMBL-EBI, European Bioinformatics
Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10
1SD, UK
2 School of Biological Sciences, The
University of Manchester, Oxford Road, Manchester, M13 9PT, UK
Received on February 5, 2001
; revised on April 1, 2001
; accepted on April 1, 2001
G protein coupled receptors (GPCRs) are found in great numbers in most eukaryotic genomes. They are responsible for sensing a staggering variety of structurally diverse ligands, with their activation resulting in the initiation of a variety of cellular signalling cascades. The physiological response that is observed following receptor activation is governed by the guanine nucleotide-binding proteins (G proteins) to which a particular receptor chooses to couple. Previous investigations have demonstrated that the specificity of the receptor-G protein interaction is governed by the intracellular domains of the receptor. Despite many studies it has proven very difficult to predict de novo , from the receptor sequence alone, the G proteins to which a GPCR is most likely to couple. We have used a data-mining approach, combining pattern discovery with membrane topology prediction, to find patterns of amino acid residues in the intracellular domains of GPCR sequences that are specific for coupling to a particular functional class of G proteins. A prediction system was then built, being based upon these discovered patterns. We can report this approach was successful in the prediction of G protein coupling specificity of unknown sequences. Such predictions should be of great use in providing in silico characterisation of newly cloned receptor sequences and for improving the annotation of GPCRs stored in protein sequence databases. Available at: http://www.ebi.ac.uk/~croning/coupling.html
Contact: croning{at}ebi.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. R. Lane, B. Powney, A. Wise, S. Rees, and G. Milligan G Protein Coupling and Ligand Selectivity of the D2L and D3 Dopamine Receptors J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 319 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Muramatsu and M. Suwa Statistical analysis and prediction of functional residues effective for GPCR-G-protein coupling selectivity Protein Eng. Des. Sel., June 1, 2006; 19(6): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wistrand, L. Kall, and E. L.L. Sonnhammer A general model of G protein-coupled receptor sequences and its application to detect remote homologs Protein Sci., March 1, 2006; 15(3): 509 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Sgourakis, P. G. Bagos, and S. J. Hamodrakas Prediction of the coupling specificity of GPCRs to four families of G-proteins using hidden Markov models and artificial neural networks Bioinformatics, November 15, 2005; 21(22): 4101 - 4106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Breitwieser G Protein-Coupled Receptor Oligomerization: Implications for G Protein Activation and Cell Signaling Circ. Res., January 9, 2004; 94(1): 17 - 27. [Abstract] [Full Text] [PDF]
|
|