9NVH

NMR structure of conotoxin k-SrXIA

9NVH の概要

• エントリーDOI: 10.2210/pdb9nvh/pdb
• NMR情報: BMRB: 31235
• 分子名称: Kappa-conotoxin SrXIA (1 entity in total)
• 機能のキーワード: conotoxin, ion channel, potassium, toxin
• 由来する生物種: Conus spurius (Alphabet cone)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3865.34

構造登録者

Melchor-Meneses, C.M.,del Rio-Portilla, F. (登録日: 2025-03-20, 公開日: 2025-05-14, 最終更新日: 2025-05-21)

主引用文献

Escobar, L.I.,Quezada Suaste, C.D.,Salvador, C.,Aparicio, D.L.,Melchor-Meneses, C.M.,Bravo-Martinez, J.,de la Rosa, V.,Lopez-Gonzalez, Z.,Del Rio-Portilla, F.
Block of Kv1 potassium channels and NMR structure of recombinant conotoxin kappa-SrXIA.
Toxicon, 262:108384-108384, 2025

PubMed Abstract: The biologically active components of Conus venoms are mainly small peptides with disulfide-bonded structures. Some conotoxins contain post-translational modifications as an evolutionary strategy to enhance their potency and selectivity towards ion channels and receptors. Few conotoxins are known to target mammalian Kv1 channels. κ-SrXIA from the venom of Conus spurius inhibits the voltage-gated potassium Kv1.2 and Kv1.6 channels through a basic ring of Arg. The 32 amino acid κ-SrXIA has eight Cys residues arranged in the pattern that defines the I-superfamily with four disulfide bridges, two gamma-carboxy-glutamates (Gla), and a Pro-amidated C-terminus (X). In this study, we obtained and determined the biological activity and NMR structure of recombinant κ-SrXIA without Gla and X. The conotoxin cDNA was expressed in E. coli CD41 and purified by GST-affinity chromatography and RP-HPLC. Pharmacological assays were performed by two-electrode voltage-clamp recordings in Xenopus laevis oocytes expressing recombinant Kv1.1, Kv1.2, Kv1.3, Kv1.4 and Kv1.6 channels. Except for Kv1.3, κ-Sr-XIA irreversibly blocked Kv1 channels displaying a lower affinity and a slower inhibition kinetics than native conotoxin. Even when κ-SrXIA displayed a high structural similarity to GXIA from the I-superfamily, the resultant disulfide connectivity forming an ICK+1 motif showed two antiparallel β-strands as ι-RXIA from the I-superfamily. This study represents the first 3D NMR structure for a member of the I-superfamily.

PubMed: 40324600
DOI: 10.1016/j.toxicon.2025.108384

実験手法

SOLUTION NMR