Natriuretic peptides appeared after their receptors in vertebrates

Fig. 1. Amino acid sequences of the tree human natriuretic peptides and the lamprey natriuretic peptide. The amino acids involved in binding are shown in red

Fig. 2. Binding of the natriuretic peptides with the a NPR1 and b NPR3 receptors retrieved from PDB structures 1yk0 and 1 t34. Receptors are in red, ligands in azul, and the amino acids involved in binding are in blue

Fig. 3. Alignment of the sequences of receptor binding pockets to human natriuretic peptide with that of hagfish. The numbers represent the position of the amino acids of the binding pocket in the human NPR1. The positions in the alignment are shown above each amino acid

Fig. 4. Phylogenetic tree of protostome (+ outgroups) guanylyl cyclase receptors. The red stars represent the outgroups. The groups generated by the tree are colored in the capture of lifemap

Fig. 5. Logos of nine natriuretic peptides found in non-vertebrate animals

Fig. 6. 3D structure of the ten peptides found in non-vertebrate animals, whose protein sequence has similarities with that of human natriuretic peptides

Fig. 7. a Superposition of the three-dimensional structure of the human natriuretic peptide with the ten peptides found in non-vertebrate animals. The human natriuretic peptide is shown in yellow. b Model of binding of the five peptides from non-vertebrate animals in a binding pocket of the human NPR3 receptor different from that occupied by of human natriuretic peptides. The receptor is represented in green, the natriuretic peptide NPPA in brown. The five peptides from each of the five non vertebrate species are represented respectively in red, blue, violet, pink and azure. c Model of binding of the five peptides from non-vertebrate animals in the same binding pocket of the human NPR3 receptor as that occupied by the human natriuretic peptides. The receptor is represented in green, the natriuretic peptide NPPA in brown. The five peptides from each of the five non-vertebrate species are respectively represented in violet, yellow, beige, pink and orange

Fig. 8. The flowchart summarizes the principal steps followed in the methodology of the article. The order by which the works were conducted is indicated by the arrows