Unusual binding mode of scorpion toxin BmKTX onto potassium channels relies on its distribution of acidic residues |
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Authors: | Zongyun Chen Youtian Hu Jun Hu Weishan Yang Jean-Marc Sabatier Michel De Waard Zhijian Cao Wenxin Li Song Han Yingliang Wu |
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Affiliation: | 1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;2. School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China;3. Center for Biodrug Research, Wuhan University, Wuhan 430072, China;4. Inserm U1097, Parc Scientifique et Technologique de Luminy, 163, avenue de Luminy, 13288 Marseille Cedex 09, France;5. Inserm U836, Grenoble Neuroscience Institute, Labex Ion Channels Science and Therapeutics, 38042 Grenoble Cedex 09, France;6. Université Joseph Fourier, Grenoble, France;g Smartox Biotechnology, avenue du Grand Sablon, 38700 La Tronche, France |
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Abstract: | Besides classical scorpion toxin–potassium channel binding modes, novel modes remain unknown. Here, we report a novel binding mode of native toxin BmKTX towards Kv1.3 channel. The combined experimental and computational data indicated that BmKTX-D33H analog used the classical anti-parallel β-sheet domain as the channel-interacting interface together with the conserved channel pore-blocking Lys26. However, the wild-type BmKTX was found to use Arg23 rather than Lys26 as the new pore-blocking residue, and mainly adopt the turn motif between the α-helix and antiparallel β-sheet domains to recognize Kv1.3 channel. Together, these findings not only reveal that scorpion toxin–potassium channel interaction modes are more diverse than thought, but also highlight the functional role of toxin acidic residues in mediating diverse toxin–potassium channel binding modes. |
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Keywords: | Scorpion toxin BmKTX Acidic residues Potassium channels BmKTX-D33H analog Binding mode Electrostatic repulsion |
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