| Autor: |
Kim YJ; Department of Advanced Toxicology Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34114, Republic of Korea., Jo Y; Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje 53201, Republic of Korea., Lee SE; Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea., Kim J; Personal Genomics Institute (PGI), Genome Research Foundation (GRF), Cheongju 28160, Republic of Korea., Choi JP; Personal Genomics Institute (PGI), Genome Research Foundation (GRF), Cheongju 28160, Republic of Korea., Lee N; Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje 53201, Republic of Korea., Won H; Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje 53201, Republic of Korea., Woo DH; Department of Advanced Toxicology Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34114, Republic of Korea., Yum S; Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje 53201, Republic of Korea.; KIOST School, University of Science and Technology, Geoje 53201, Republic of Korea. |
| Abstrakt: |
We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues ( 3 Asp, 25 Lys, and 34 Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3 Glu, 25 Arg, and 34 Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts. |
