Molecular Information of charybdotoxin blockade in the large conductance calcium-activated potassium channel.
The scorpion toxin, charybdotoxin (ChTX), is the first identified peptide inhibitor for the large-conductance Ca2+ and voltage-dependent K+ (BK) channel, and the chemical information of the interaction between ChTX and BK channel remains unclear today. Using combined computational methods, we obtained a ChTX-BK complex structure model, which correlated well with the mutagenesis data. In this complex, ChTX mainly used its beta-sheet domains to associate the BK channel with a conserved pore-blocking Lys27. Another crucial Tyr36 residue of ChTX lied over the loop connecting selectivity filter and S6 helix of BK channel, forming a hydrogen bond with Gly291 of BK channel. Besides, the unique turret region of BK channel was found to be far away from bound ChTX, which could explain the fact that many BK channel blockers show less selectivity over Kv channels. Together, all these information is helpful to reveal the diverse interactions between scorpion toxins and potassium channels and can accelerate the molecular engineering of specific inhibitor design.
Qiu
Su
S
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
Yi
Hong
H
Liu
Hui
H
Cao
Zhijian
Z
Wu
Yingliang
Y
Li
Wenxin
W
D000595:Amino Acid Sequence; D000818:Animals; D018999:Charybdotoxin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012605:Scorpions / Q000378:metabolism*; D016415:Sequence Alignment; D013816:Thermodynamics
D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D018999:Charybdotoxin