Abstract
Yellow-related proteins (YRPs) present in sand fly saliva act as affinity binders of bioamines, and help the fly to complete a bloodmeal by scavenging the physiological signals of damaged cells. They are also the main antigens in sand fly saliva and their recombinant form is used as a marker of host exposure to sand flies. Moreover, several salivary proteins and plasmids coding these proteins induce strong immune response in hosts bitten by sand flies and are being used to design protecting vaccines against Leishmania parasites. In this study, thirty two 3D models of different yellow-related proteins from thirteen sand fly species of two genera were constructed based on the known protein structure from Lutzomyia longipalpis. We also studied evolutionary relationships among species based on protein sequences as well as sequence and structural variability of their ligand-binding site. All of these 33 sand fly YRPs shared a similar structure, including a unique tunnel that connects the ligand-binding site with the solvent by two independent paths. However, intraspecific modifications found among these proteins affects the charges of the entrances to the tunnel, the length of the tunnel and its hydrophobicity. We suggest that these structural and sequential differences influence the ligand-binding abilities of these proteins and provide sand flies with a greater number of YRP paralogs with more nuanced answers to bioamines. All these characteristics allow us to better evaluate these proteins with respect to their potential use as part of anti-Leishmania vaccines or as an antigen to measure host exposure to sand flies.
Highlights
During intake of a bloodmeal, sand flies (Diptera: Phlebotominae) and other bloodsucking insects inject saliva into the host skin
Thirty two sand fly salivary Yellow-related proteins (YRPs) were identified based on their similarity with PDB ID: 3Q6K from L. longipalpis [26], the only known 3D structure of YRPs of phlebotominae sand flies
These YRPs were detected in all 13 sand fly species with a published salivary gland transciptome: 9 Phlebotomus species from 5 subgenera (Phlebotomus, Paraphlebotomus, Larroussius, Adlerius, and Euphlebotomus), and 4 Lutzomyia species from 3 subgenera (Lutzomyia, Nyssomyia, and Helcocyrtomyia)
Summary
During intake of a bloodmeal, sand flies (Diptera: Phlebotominae) and other bloodsucking insects inject saliva into the host skin. This saliva contains a mixture of various proteins, which play a major role in preventing host haemostatic and inflammatory responses of different pathways, e.g. platelet activation, coagulation, inflammation, mast cell function, and vasoconstriction (reviewed in [1]). The vectors of Leishmania protozoan parasites, these salivary proteins have been studied for decades due to their biological activities and possible. Yellow-Related Proteins of Sand Flies design, data collection and analysis, decision to publish, or preparation of the manuscript
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