Homology modeling and molecular docking studies of kisspeptins and their receptors in pejerrey fish.

ALEJANDRO S. MECHALY; ALEJANDRO GIORGETTI; OSWALDO TOVAR; ARIEL E. MECHALY; JORDI VIÑAS; GUSTAVO M. SOMOZA

Buenos Aires

Congreso; 4th ISCB-LA Conference-7th Argentinian Congress of Bioinformatics and Computational Biology.; 2016

ISCB-LA

Kisspeptin receptors (Kissrs) constitute a family of G Protein-Coupled Receptors that bind kisspeptin to regulate GnRH release in vertebrates. In pejerrey fish, Odontesthes bonariensis two receptors -Kissr2 and Kissr3- are respectively activated by two ligands, kiss2 and kiss1. Gene expression tissue distribution studies revealed the presence of two splicing variants for both receptors, originated by the retention of intron 3 for kissr2 gene and the retention of intron 4 for kissr3. In the case of kissr2 the retention of intron 3 introduces a premature stop codon that lead to a putatively truncate protein, whereas in the case of kissr3 the intron retention produces a shift that leads to a stop codon in exon 5. In this study, we built 3D models of the receptors in complex with their cognate ligands to evaluate the potential impact of alternative splicing on their functionality. Receptors and their ligands were modeled and docked using the on-line platform GOMoDo (http://molsim.sci.univr.it/cgibin/cona/begin.php). The structural analysis of the Kissr2 and Kissr3 homology models indicates that the truncations certainly lead to non-functional receptors, as the polypeptide fragments that are missing are fundamental to build the kisspeptin-binding cavity. The results of this analysis can be extended to other teleost fish species, as similar mechanisms of intron retention resulting in truncated splicing variants of these genes were observed.