In-silico characterization and evolutionary analysis of conserved GPI-anchored protein SGU (Secretory Glycoconjugate of Unknownfunction) in Anopheles gambiae

Abstract

To control malaria, researchers are focused on immunogenic protein to develop a vaccine against this life-threatening disease. The target immunogenic proteins against parasite infection and other diseases are mostly focused on GPI-anchor proteins. AgSGU is secretory glycoconjugate, the second most expressed protein in mosquito midgut after blood feeding. Recent studies confirmed that Pfs47 is the key protein for ookinetes invasion in the mosquito midgut and AGAP006398 act as a receptor for Pfs47. Protein interaction pathway analysis using bioinformatics approaches shows that AgSGU makes a complex with AGAP006398 and Pfs47, so here we target AgSGU protein for its functional and molecular characterization. Blastp analysis showing its conservancy in most Anopheles mosquito species. Phylogenetic evolutionary analysis shows that AgSGU is an independently evolved protein and closely related to ACON000570 in Anopheles coluzzii. Domain architecture analysis results that it is composed of a single MBF2 domain which acts as a transcriptional activator factor. The 3-D structure was prepared by I-TASSER and refined with the Galaxy Refine tool. The calculated RMSD value for the predicted structure was 0.558, suggesting the reliability of the 3-D structure. AgSGU was docked with AGAP006398 and Pfs47 and interacted effectively with both the protein. The antigenicity evaluation confirmed its potential to activate the immune response. The C-ImmSim immune response analysis proved that AgSGU protein activates both humoral and acquired immune responses. Finally, these studies conclude that AgSGU protein is a potential target for developing a transmission-blocking vaccine against malaria.