Modelling and functional prediction of two paralogous kisspeptin receptors, kissr2 and kissr3, in pejerrey fish.

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

Gothenburg

Congreso; 8th International Symposium on Fish Endocrinology.; 2016

The kisspeptin system has a main role in the control of puberty in mammals and it is composed by the neuropeptide, KISS, and its associated receptor, KISSR. However, in teleost fish species two kissr paralog genes have been identified. Here, we report the gene organization and the in silico structural analysis of two receptors, kissr2 and kissr3, in the pejerrey, Odontesthes bonariensis. The kissr2 gene in pejerrey comprises five exons and four introns and kissr3 presented six exons and five introns. The organ/tissue distribution expression analysis evidenced two distinct transcripts for both receptors. The kissr2 contained an insert of 98 nucleotides caused by the retention of the whole intron III and kissr3 an insertion of 79 nucleotides product of the whole intron IV retention. In kissr2 the predicted amino-acidic sequence comprises one premature termination codons in transmembrane helix 4; in the case of kissr3, there is a shift in the reading frame at the intratracellular domain 3, leading to the loss of TM6 and TM7, which may result in a non-functional truncated receptor. Molecular modelling of the Kissr2 and Kissr3 3D structure were performed by the on-line platform GOMoDo. Both receptors were then analyzed by a virtual docking protocol included in the GOMoDo server. Indeed, the docking procedure was performed by the Haddock program version accessible through the server. The predicted binding cavity in both, Kissr2 and Kissr3 is formed by residues of TM3, TM5, TM6 and TM7. Remarkably, almost all the identified residues are conserved in vertebrates. The lack of TMs 4 and 5 upon the insertion of premature stop codons will cause not only the lost of the binding cavity but also fundamental regions for the stability of the protein structure. In conclusion, the reported alternative splicing events might contribute to regulative mechanism of the Kiss/Kissr-signalling pathways.