Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug | Zendy

Anu Tyagi | Zendy; Tofayel Ahmed | Zendy; Shi Jian | Zendy; Saumya Bajaj | Zendy; Seow Theng Ong | Zendy; Stephanie Shee Min Goay | Zendy; Yue Zhao | Zendy; Igor Vorobyov | Zendy; Changlin Tian | Zendy; K. George Chandy | Zendy; Shashi Bhushan | Zendy

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Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug

Author(s) -

Anu Tyagi,

Tofayel Ahmed,

Shi Jian,

Saumya Bajaj,

Seow Theng Ong,

Stephanie Shee Min Goay,

Yue Zhao,

Igor Vorobyov,

Changlin Tian,

K. George Chandy,

Shashi Bhushan

Publication year - 2022

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2113536119

Subject(s) - depolarization , selectivity , biophysics , chemistry , potassium channel , peptide , voltage gated potassium channel , cryo electron microscopy , ion channel , membrane , biochemistry , biology , receptor , catalysis

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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