Abstract
BackgroundIn mammals, the natriuretic system contains three natriuretic peptides, NPPA, NPPB and NPPC, that bind to three transmembrane receptors, NPR1, NPR2 and NPR3. The natriuretic peptides are known only in vertebrates. In contrast, the receptors have orthologs in all the animal taxa and in plants. However, in non-vertebrates, these receptors do not have natriuretic properties, and most of their ligands are unknown. How was the interaction of the NP receptors and the NP established in vertebrates? Do natriuretic peptides have orthologs in non-vertebrates? If so, what was the function of the interaction? How did that function change? If not, are the NP homologous to ancestral NPR ligands? Or did the receptor’s binding pocket completely change during evolution?MethodsIn the present study, we tried to determine if the pairs of natriuretic receptors and their ligands come from an ancestral pair, or if the interaction only appeared in vertebrates. Alignments, modeling, docking, research of positive selection, and motif research were performed in order to answer this question.ResultsWe discovered that the binding pocket of the natriuretic peptide receptors was completely remodeled in mammals. We found several peptides in non vertebrates that could be related to human natriuretic peptides, but a set of clues, as well as modeling and docking analysis, suggest that the natriuretic peptides undoubtedly appeared later than their receptors during animal evolution. We suggest here that natriuretic peptide receptors in non vertebrates bind to other ligands.ConclusionsThe present study further support that vertebrate natriuretic peptides appeared after their receptors in the tree of life. We suggest the existence of peptides that resemble natriuretic peptides in non-vertebrate species, that might be the result of convergent evolution.
Highlights
In mammals, the natriuretic system contains three natriuretic peptides, Natriuretic peptide A (NPPA), Natriuretic peptide B (NPPB) and Natriuretic peptide C (NPPC), that bind to three transmembrane receptors, Natriuretic peptide receptor 1 (NPR1), Natriuretic peptide receptor 2 (NPR2) and Natriuretic peptide receptor 3 (NPR3)
In mammals, the natriuretic system is composed of three peptides, the natriuretic peptide A named ANP, natriurtic peptide B (BNP) and natriuretic peptide C (CNP), called NPPA, NPPB and NPPC, that bind to membrane receptors, NPR1, 2 and 3
Positive selection on guanylyl cyclase receptor binding pockets According to our results, only one tree had indexes of positive selection: the phylogenetic tree of Protostomes, that included outgroup branches
Summary
The natriuretic system contains three natriuretic peptides, NPPA, NPPB and NPPC, that bind to three transmembrane receptors, NPR1, NPR2 and NPR3. In non-vertebrates, these receptors do not have natriuretic properties, and most of their ligands are unknown. The natriuretic system is composed of three peptides, the natriuretic peptide A named ANP, natriurtic peptide B (BNP) and natriuretic peptide C (CNP), called NPPA, NPPB and NPPC, that bind to membrane receptors, NPR1, 2 and 3. The natriuretic peptides were discovered thanks to their diuretic properties [2, 3] They are involved in other processes [4], such as cell proliferation, angiogenesis, apoptosis, inflammation [5], control of lipid metabolism [6], and meiotic arrest [7]. Each of the three peptides has cysteines separating 15 amino acids, and joined together to form a cysteine bridge, giving the peptide a loop structure (Fig. 1)
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