TY - JOUR
T1 - Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes
AU - Jablonka, Willy
AU - Kim, Il Hwan
AU - Alvarenga, Patricia H.
AU - Valenzuela, Jesus G.
AU - Ribeiro, Jose M.C.
AU - Andersen, John F.
N1 - Funding Information:
The similarity of the long-form D7s, and especially the eicosanoid-binding N-terminal domains in mosquito and sand fly saliva, suggest that they have evolved from the same, or a very similar two-domain common ancestor, but the independent evolution of blood feeding in the two groups implies that selectivity for vertebrate eicosanoid ligands must have evolved independently. This is supported by the differences in exon structure in the mosquito and sand fly D7 genes. The molecular progenitor of the salivary D7 proteins is not known, but recently, mJHBP a non-salivary two-domain D7-like protein has been identified throughout the mosquito family and is the first protein of this type synthesized outside of the salivary gland15. This protein was found to circulate in the hemolymph of male and female adults and specifically binds JH at a comparable site in the N-terminal domain of the protein. The protein binds JH in the N-terminal domain pocket, while the terminal helix α13 of the C-terminal domain forms a cap-like structure that buries the ligand. However, no orthologs of this protein have been found in insects outside of the mosquito family, including the sand flies, making it unlikely to serve as a direct progenitor of the salivary D7s in both groups. Interestingly, the intron-exon structure of this gene differs from both the mosquito and sand fly salivary D7 genes.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The habit of blood feeding evolved independently in many insect orders of families. Sand flies and mosquitoes belong to separate lineages of blood-feeding Diptera and are thus considered to have evolved the trait independently. Because of this, sand fly salivary proteins differ structurally from those of mosquitoes, and orthologous groups are nearly impossible to define. An exception is the long-form D7-like proteins that show conservation with their mosquito counterparts of numerous residues associated with the N-terminal domain binding pocket. In mosquitoes, this pocket is responsible for the scavenging of proinflammatory cysteinyl leukotrienes and thromboxanes at the feeding site. Here we show that long-form D7 proteins AGE83092 and ABI15936 from the sand fly species, Phlebotomus papatasi and P. duboscqi, respectively, inhibit the activation of platelets by collagen and the thromboxane A 2 analog U46619. Using isothermal titration calorimetry, we also demonstrate direct binding of U46619 and cysteinyl leukotrienes C 4 , D 4 and E 4 to the P. papatasi protein. The crystal structure of P. duboscqi ABI15936 was determined and found to contain two domains oriented similarly to those of the mosquito proteins. The N-terminal domain contains an apparent eicosanoid binding pocket. The C-terminal domain is smaller in overall size than in the mosquito D7s and is missing some helical elements. Consequently, it does not contain an obvious internal binding pocket for small-molecule ligands that bind to many mosquito D7s. Structural similarities indicate that mosquito and sand fly D7 proteins have evolved from similar progenitors, but phylogenetics and differences in intron/exon structure suggest that they may have acquired the ability to bind vertebrate eicosanoids independently, indicating a convergent evolution scenario.
AB - The habit of blood feeding evolved independently in many insect orders of families. Sand flies and mosquitoes belong to separate lineages of blood-feeding Diptera and are thus considered to have evolved the trait independently. Because of this, sand fly salivary proteins differ structurally from those of mosquitoes, and orthologous groups are nearly impossible to define. An exception is the long-form D7-like proteins that show conservation with their mosquito counterparts of numerous residues associated with the N-terminal domain binding pocket. In mosquitoes, this pocket is responsible for the scavenging of proinflammatory cysteinyl leukotrienes and thromboxanes at the feeding site. Here we show that long-form D7 proteins AGE83092 and ABI15936 from the sand fly species, Phlebotomus papatasi and P. duboscqi, respectively, inhibit the activation of platelets by collagen and the thromboxane A 2 analog U46619. Using isothermal titration calorimetry, we also demonstrate direct binding of U46619 and cysteinyl leukotrienes C 4 , D 4 and E 4 to the P. papatasi protein. The crystal structure of P. duboscqi ABI15936 was determined and found to contain two domains oriented similarly to those of the mosquito proteins. The N-terminal domain contains an apparent eicosanoid binding pocket. The C-terminal domain is smaller in overall size than in the mosquito D7s and is missing some helical elements. Consequently, it does not contain an obvious internal binding pocket for small-molecule ligands that bind to many mosquito D7s. Structural similarities indicate that mosquito and sand fly D7 proteins have evolved from similar progenitors, but phylogenetics and differences in intron/exon structure suggest that they may have acquired the ability to bind vertebrate eicosanoids independently, indicating a convergent evolution scenario.
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U2 - 10.1038/s41598-019-41848-0
DO - 10.1038/s41598-019-41848-0
M3 - Article
C2 - 30926880
AN - SCOPUS:85063772635
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 5340
ER -