Rearrangement of a Unique Kv1.3 Selectivity Filter Conformation Upon Binding of a Drug
Proceedings of the National Academy of Sciences of the United States of America（2022）SCI 1区
Nanyang Technol Univ | Max Planck Inst Biophys | Natl Univ Singapore | LKCMedicine-ICESing Ion Channel Platform | Univ Sci & Technol China | Univ Calif Davis
Abstract
Significance Voltage-gated potassium channels (Kv) open with membrane depolarization and allow the flow of K + ions. Ion flow is tightly governed by time-dependent entry into nonconducting inactivated states. Here, we focus on Kv1.3, a channel of physiological importance in immune cells. We used cryogenic electron microscopy to determine structures of human Kv1.3 alone and bound to dalazatide, a peptide inhibitor in human trials. In the unbound state, Kv1.3’s outer pore is rearranged compared to all other K + channels analyzed. Interaction of dalazatide with Kv1.3’s outer pore causes a dynamic rearrangement of the selectivity filter as Kv1.3 enters a drug-blocked state.
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Key words
ion channels,potassium channels,selectivity filter,ShK,dalazatide
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