The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea

BMC Genomics

Research Article

Paul McVeigh¹  Aaron G Maule¹  Tim A Day²  Steve A Carlson²  Michael J Kimber²  Mostafa Zamanian² 

[1] Biomolecular Processes, School of Biological Sciences, Queen's University Belfast, Belfast, UK;Department of Biomedical Sciences, Iowa State University, Ames, IA, USA;Neuroscience Program, Iowa State University, Ames, IA, USA;

关键词: Support Vector Machine;    Hide Markov Model;    Secretin;    Training Sequence;    Support Vector Machine Training;   

DOI  :  10.1186/1471-2164-12-596

 received in 2011-03-31, accepted in 2011-12-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundG protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum.ResultsApplication of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification.ConclusionsGenome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.

【 授权许可】

CC BY   
© Zamanian et al; licensee BioMed Central Ltd. 2011