Insights from the analysis of conserved motifs and permitted amino acid exchanges in the human, the fly and the worm GPCR clusters

G-protein coupled receptors (GPCRs) belong to biologically important and functionally diverse and largest super family of membrane proteins. GPCRs retain a characteristic membrane topology of seven alpha helices with three intracellular, three extracellular loops and flanking N' and C' terminal residues. Subtle differences do exist in the helix boundaries (TM-domain), loop lengths, sequence features such as conserved motifs, and substituting amino acid patterns and their physiochemical properties amongst these sequences (clusters) at intra-genomic and inter-genomic level (please re-phrase into 2 statements for clarity). In the current study, we employ prediction of helix boundaries and scores derived from amino acid substitution exchange matrices to identify the conserved amino acid residues (motifs) as consensus in aligned set of homologous GPCR sequences. Co-clustered GPCRs from human and other genomes, organized as 32 clusters, were employed to study the amino acid conservation patterns and species-specific or cluster-specific motifs. Critical analysis on sequence composition and properties provide clues to connect functional relevance within and across genome for vast practical applications such as design of mutations and understanding of disease-causing genetic abnormalities

Cross-Genome Clustering of Human and G-Protein Coupled Receptors

G-protein coupled receptors (GPCRs) are one of the largest groups of membrane proteins and are popular drug targets. The work reported here attempts to perform cross-genome phylogeny on GPCRs from two widely different taxa, human versus C. elegans genomes and to address the issues on evolutionary plasticity, to identify functionally related genes, orthologous relationship, and ligand binding properties through effective bioinformatic approaches. Through RPS blast around 1106 nematode GPCRs were given chance to associate with previously established 8 types of human GPCR profiles at varying E -value thresholds and resulted 32 clusters were illustrating co-clustering and class-specific retainsionship. In the significant thresholds, 81% of the C. elegans GPCRs were associated with 32 clusters and 27 C. elegans GPCRs (2%) inferred for orthology. 177 hypothetical proteins were observed in cluster association and could be reliably associated with one of 32 clusters. Several nematode-specific GPCR clades were observed suggesting lineage-specific functional recruitment in response to environment

DOR – a Database of Olfactory Receptors – Integrated Repository for Sequence and Secondary Structural Information of Olfactory Receptors in Selected Eukaryotic Genomes

Olfaction is the response to odors and is mediated by a class of membrane-bound proteins called olfactory receptors (ORs). An understanding of these receptors serves as a good model for basic signal transduction mechanisms and also provides important clues for the strategies adopted by organisms for their ultimate survival using chemosensory perception in search of food or defense against predators. Prior research on cross-genome phylogenetic analyses from our group motivated the addressal of conserved evolutionary trends, clustering, and ortholog prediction of ORs. The database of olfactory receptors (DOR) is a repository that provides sequence and structural information on ORs of selected organisms (such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus , and Homo sapiens ). Users can download OR sequences, study predicted membrane topology, and obtain cross-genome sequence alignments and phylogeny, including three-dimensional (3D) structural models of 100 selected ORs and their predicted dimer interfaces. The database can be accessed from http://caps.ncbs.res.in/DOR . Such a database should be helpful in designing experiments on point mutations to probe into the possible dimerization modes of ORs and to even understand the evolutionary changes between different receptors