Unusual binding mode of scorpion toxin BmKTX onto potassium channels relies on its distribution of acidic residues.
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 Lys(26). However, the wild-type BmKTX was found to use Arg(23) rather than Lys(26) 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.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; Center for Biodrug Research, Wuhan University, Wuhan 430072, China.
Zongyun
Z
Chen
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Youtian
Y
Hu
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Jun
J
Hu
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Weishan
W
Yang
Inserm U1097, Parc Scientifique et Technologique de Luminy, 163, avenue de Luminy, 13288 Marseille Cedex 09, France.
Jean-Marc
JM
Sabatier
Inserm U836, Grenoble Neuroscience Institute, Labex Ion Channels Science and Therapeutics, 38042 Grenoble Cedex 09, France; Université Joseph Fourier, Grenoble, France; Smartox Biotechnology, avenue du Grand Sablon, 38700 La Tronche, France.
Michel
M
De Waard
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Zhijian
Z
Cao
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; Center for Biodrug Research, Wuhan University, Wuhan 430072, China.
Wenxin
W
Li
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: Hansong@whu.edu.cn.
Song
S
Han
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; Center for Biodrug Research, Wuhan University, Wuhan 430072, China. Electronic address: ylwu@whu.edu.cn.
Yingliang
Y
Wu
D000595:Amino Acid Sequence; D003198:Computer Simulation; D057809:HEK293 Cells; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008958:Models, Molecular; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000235:genetics / Q000378:metabolism*
C109066:KTX toxin, Buthus; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms
Acidic residues; Binding mode; BmKTX-D33H analog; Electrostatic repulsion; Potassium channels; Scorpion toxin BmKTX