Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin (NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., N-terminal, loops 1-4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a (Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4, and the C-terminal primarily interacted with the S3-S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7. Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.
动物毒腺中含有多种抑制钠离子通道Nav1.7的多肽毒素，包括来自蜘蛛的NaSpTx家族I毒素。NaSpTx家族I中的毒素具有N-末端、环1-4和C-末端等共同结构。在该文中，我们以多肽Ca2a为模板研究了NaSpTx家族I中毒素作用于Nav1.7的共用特性。该家族毒素在作用于Nav1.7之前，通过相似的疏水残基与细胞膜表面发生相互作用。位于环1、环4和C-末端的残基则主要与结构域II中的S3-S4之间的功能域相互作用，尤其与碱性氨基酸E818结合。我们发现Ca2a中的环2在其与Nav1.7的相互作用中具有关键效力。我们的研究进一步证明NaSpTx家族I毒素不仅具有相似的结构，同时发现其在与Nav1.7作用时利用共同的机制。.
Keywords: ICK motif; Nav1.7; Peptide toxin; Spider.