Figure 4.

Multiple sequence alignment of spider knottins targeting Site 4 and Site 3 in Na_V channels. The NaSpTx family 1–3 generally target Site 4 to inhibit channel activity, except Hm1a which targets Site 3 to excite the channel [20]. JzTx-14 [125] from NaSpTx7 targets Site 4 and inhibits the channel, whereas JzTx-I [100] and JzTx-II [98] from NaSpTx7 targets Site 3 to excite the channel. Yellow highlights conserved cysteines, green highlights hydrophobic residues, cyan indicates positively charged residues, red indicates negatively charged residues and bold letter indicates the aromatic residues. The “*” indicates identical residues, “:” indicates strong conservation, “.” indicates weak conservation.