Data from: Trans-toxin ion-sensitivity of charybdotoxin-blocked potassium-channels reveals unbinding transitional states
Data files
Jul 24, 2019 version files 371.77 MB
-
Fig 2 selectivity -1.xlsx
-
Fig 2 traces.xlsx
-
Fig 3 potassium sensitivity.xlsx
-
Fig 4 No memory.xlsx
-
Fig 5 F425F inhibition and fits.xlsx
-
Fig 6 V-dep of Tonic and open inhibition.xlsx
-
movieFinalTox8.mp4
-
No memory aditional experiments.pdf
-
Shaker-CTX MD (V).zip
-
Shaker-CTX MD.zip
Abstract
In-silico and in-vitro studies have made progress in understanding protein-protein complexes formation; however, the molecular mechanisms for their dissociation are unclear. Protein-protein complexes, lasting from microseconds to years, often involve induced-fit, challenging computational or kinetic analysis. Charybdotoxin (CTX), a peptide from the Leiurus scorpion venom, blocks voltage-gated K+-channels in a unique example of binding/unbinding simplicity. CTX plugs the external mouth of K+-channels pore, stopping K+-ion conduction, without inducing conformational changes. Conflicting with a tight binding, we show that external permeant ions enhance CTX-dissociation, implying a path connecting the pore, in the toxin-bound channel, with the external solution. This sensitivity is explained if CTX wobbles between several bound conformations, producing transient events that restore the electrical and ionic trans-pore gradients. Wobbling may originate from a network of contacts in the interaction interface that are in dynamic stochastic equilibria. These partially-bound intermediates could lead to distinct, and potentially manipulable, dissociation pathways.