The tarantula toxin GxTx detains K⁺ channel gating charges in their resting conformation.

ABSTRACT: Allosteric ligands modulate protein activity by altering the energy landscape of conformational space in ligand-protein complexes. Here we investigate how ligand binding to a K⁺ channel's voltage sensor allosterically modulates opening of its K⁺-conductive pore. The tarantula venom peptide guangxitoxin-1E (GxTx) binds to the voltage sensors of the rat voltage-gated K⁺ (Kv) channel Kv2.1 and acts as a partial inverse agonist. When bound to GxTx, Kv2.1 activates more slowly, deactivates more rapidly, and requires more positive voltage to reach the same K⁺-conductance as the unbound channel. Further, activation kinetics are more sigmoidal, indicating that multiple conformational changes coupled to opening are modulated. Single-channel current amplit

SUBMITTER: Tilley DC 

PROVIDER: S-EPMC6400525 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature