Fig. 6.

Hypothetical model for the role of enolase in ookinete midgut invasion. (Left, No SM1 peptide) About midway in their development in the mosquito midgut, ookinetes start expressing enolase on their surface (Fig. S4). (Right) Plasminogen from the surrounding blood meal (Figs. 4 and 5A and Figs. S6 and S7) is captured by the 6-aa C-terminal lysine domain of enolase (lysine motif). Plasminogen is subsequently converted into active plasmin (Fig. 5B), a broad-spectrum serine protease, thus promoting the hydrolysis of glycocalyx components. Local breach of glycocalyx integrity facilitates ookinete access to the midgut epithelium and interaction of a separate enolase domain (SM1-like domain) with a putative midgut receptor, thus promoting invasion. SM1 peptide (+SM1 peptide) mimics the SM1-like domain of enolase [anti-SM1 antibody recognizes enolase (Fig. 1B and Fig. S3) and competes with it for binding to the putative midgut receptor]. When the midgut receptors are occupied by the SM1 peptide, interaction with enolase on the surface of the ookinete is abrogated and invasion is aborted.