Prediction of the coupling specificity of G protein coupled receptors to their G proteins

Abstract 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: [email protected]</jats:p

Transcriptome analysis for the chicken based on 19,626 finished cDNA sequences and 485,337 expressed sequence tags

We present an analysis of the chicken (Gallus gallus) transcriptome based on the full insert sequences for 19,626 cDNAs, combined with 485,337 EST sequences. The cDNA data set has been functionally annotated and describes a minimum of 11,929 chicken coding genes, including the sequence for 2260 full-length cDNAs together with a collection of noncoding (nc) cDNAs that have been stringently filtered to remove untranslated regions of coding mRNAs. The combined collection of cDNAs and ESTs describe 62,546 clustered transcripts and provide transcriptional evidence for a total of 18,989 chicken genes, including 88% of the annotated Ensembl gene set. Analysis of the ncRNAs reveals a set that is highly conserved in chickens and mammals, including sequences for 14 pri-miRNAs encoding 23 different miRNAs. The data sets described here provide a transcriptome toolkit linked to physical clones for bioinformaticians and experimental biologists who wish to use chicken systems as a low-cost, accessible alternative to mammals for the analysis of vertebrate development, immunology, and cell biology