| Autor: |
Karbat, Izhar, Altman-Gueta, Hagit, Fine, Shachar, Szanto, Tibor, Hamer-Rogotner, Shelly, Dym, Orly, Frolow, Felix, Gordon, Dalia, Panyi, Gyorgy, Gurevitz, Michael, Reuveny, Eitan |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 9/10/2019, Vol. 116 Issue 37, p18700-18709, 10p |
| Abstrakt: |
Voltage-dependent potassium channels (Kvs) gate in response to changes in electrical membrane potential by coupling a voltagesensing module with a K+-selective pore. Animal toxins targeting Kvs are classified as pore blockers, which physically plug the ion conduction pathway, or as gating modifiers, which disrupt voltage sensor movements. A third group of toxins blocks K+ conduction by an unknown mechanism via binding to the channel turrets. Here, we show that Conkunitzin-S1 (Cs1), a peptide toxin isolated from cone snail venom, binds at the turrets of Kv1.2 and targets a network of hydrogen bonds that govern water access to the peripheral cavities that surround the central pore. The resulting ectopic water flow triggers an asymmetric collapse of the pore by a process resembling that of inherent slow inactivation. Pore modulation by animal toxins exposes the peripheral cavity of K+ channels as a novel pharmacological target and provides a rational framework for drug design. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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