9E94

Cryo-EM structure of human TWIK-2 at pH 7.5

9E94 の概要

• エントリーDOI: 10.2210/pdb9e94/pdb
• EMDBエントリー: 47768
• 分子名称: Potassium channel subfamily K member 6, DECANE, POTASSIUM ION (3 entities in total)
• 機能のキーワード: potassium ion channel k2p, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68663.49

構造登録者

Ma, Q.,Kumar, A.,Navratna, V.,Mosalaganti, S. (登録日: 2024-11-07, 公開日: 2026-02-11)

主引用文献

Ma, Q.,Hernandez, C.C.,Navratna, V.,Kumar, A.,Rana, J.K.,Zong, J.,Lee, A.,Mosalaganti, S.
Insights into the structure and modulation of human TWIK-2.
Nat Commun, 2026

PubMed Abstract: The Tandem of pore domain in a Weak Inward Rectifying K channel 2 (TWIK-2; KCNK6) is a member of the Two-Pore Domain K (K) channel family, which is associated with pulmonary hypertension, lung injury, and inflammation. Despite its physiological relevance, the structure, regulatory mechanisms, and selective modulators of TWIK-2 remain largely unknown. Here, we present a 3.7 Å single particle cryo-electron microscopy structure of human TWIK-2 and highlight its conserved and distinctive features. Using automated whole-cell patch clamp recordings, we demonstrate that gating in TWIK-2 is voltage-dependent and insensitive to changes in the extracellular pH. We identify key residues that influence TWIK-2 activity by employing site-directed mutagenesis and provide insights into the possible lipid-mediated mechanism of TWIK-2 regulation. Additionally, we demonstrate the application of high-throughput automated whole-cell patch clamp platforms to screen small molecule modulators of TWIK-2. Our work serves as a foundation for designing high-throughput small molecule screening campaigns to identify specific high-affinity TWIK-2 modulators, including promising- anti-inflammatory therapeutics.

PubMed: 41617707
DOI: 10.1038/s41467-026-69072-1

実験手法

ELECTRON MICROSCOPY (3.67 Å)