Comparison of helminth VALs.

(A) The sequences of helminth VALs with known structure (see below) are aligned with clustalW2, and the secondary structural features are illustrated with the coordinates of Bm-VAL-1 and Hp-VAL-4 using ESPript. The different secondary structural elements shown are alpha helices as large squiggles labeled (α), 3₁₀-helices as small squiggles labeled (η), beta strands as arrows (β), and beta turns (TT). Identical residues are highlighted in solid red, and conserved residues are shown in red. The locations of the cysteine residues involved in disulfide bonds are numbered in green. The location of the CBM loop is shown in blue. The position of amino acid residues constituting the CAP tetrad are marked with a black box. (B) Bm-VAL-1 is given as a representative structure in which the different binding cavities are indicated. The CBM loop is depicted in red, and coordination of the divalent cation Zn²⁺ is shown in green. Superimposed structures of helminths VALs with a single CAP domain are given to illustrate structural differences among the different family members. The represented structures are Na-ASP-2 in blue [13], Oo-ASP-1 in orange [15], Ac-ASP-7 in cyan [90], Sm-VAL-4 in yellow [44], Hp-VAL-4 in red [12], and Bm-VAL-1 in gray [16]. ASP, activation-associated secreted protein; CAP, cysteine-rich secretory proteins/antigen 5/pathogenesis-related 1; CBM, caveolin-binding motif; VAL, venom allergen-like proteins.