Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite - PubMed
5 hours ago
- #scabies
- #ion channel
- #ivermectin
- Study focuses on a pH-sensitive pentameric ligand-gated ion channel (SsCl) from the Sarcoptes scabiei mite.
- SsCl is modulated by ivermectin, a drug facing emerging resistance issues in treating scabies.
- Cryo-EM and electrophysiology reveal SsCl structures in closed (pH 6.5) and desensitized (pH 9) states, including ivermectin-bound conformations.
- The desensitized structure shows an unexpected hourglass shape, suggesting a gating mechanism similar to cation-selective channels.
- Extracellular histidine and glutamic acid residues are identified as key to pH sensitivity.
- Ivermectin enhances open-state prevalence at pH 9 and enables atypical activation at pH 6.5.
- Findings provide insights for designing next-generation antiparasitic drugs targeting SsCl.