Ce1 and Ce4 peptides from Centruroides elegans venom were identified as high-affinity (Kd of 10 and 30 pM) and selective blockers for the Kv1.2 potassium channel using newly engineered fluorescent probes.
New fluorescent probes and selective blockers (Ce1 and Ce4) with high affinity for the Kv1.2 channel were developed, providing tools for neuroscience and neuropharmacology research.
Advanced molecular probes are required to study the functional activity of the Kv1.2 potassium channel in normal and pathological conditions. To address this, a fully active Kv1.2 channel fused with fluorescent protein mKate2 (K-Kv1.2) was engineered that has high plasma membrane presentation due to the S371T substitution, and hongotoxin 1 (HgTx1) fused with eGFP at the C-terminus (HgTx-G) was produced. HgTx-G and HgTx1 N-terminally labeled with Atto488 fluorophore were shown to be fluorescent probes of Kv1.2 in cells with dissociation constants (Kd) of 120 and 80 pM, respectively. K-Kv1.2 and HgTx-G were used as components of an analytical system to study peptide blockers of the channel and helped to find out that Ce1 and Ce4 peptides from Centruroides elegans venom possess high affinity (Kd of 10 and 30 pM) and selectivity for Kv1.2. Using molecular docking and molecular modeling techniques, the complexes of Kv1.2 with HgTx1, Ce1, and Ce4 were modeled, and determinants of the high affinity binding were proposed. New fluorescent probes and selective blockers of Kv1.2 can be used to resolve Kv1.2-related challenges in neuroscience and neuropharmacology.
Ignatova et al. (Wed,) conducted a other in Kv1.2 potassium channel function. Ce1 and Ce4 peptides was evaluated on Binding affinity (Kd) to Kv1.2 channel. Ce1 and Ce4 peptides from Centruroides elegans venom were identified as high-affinity (Kd of 10 and 30 pM) and selective blockers for the Kv1.2 potassium channel using newly engineered fluorescent probes.