8VT9

WT SthK in the presence of PIP2 and cAMP

8VT9 の概要

• エントリーDOI: 10.2210/pdb8vt9/pdb
• EMDBエントリー: 43520
• 分子名称: Transcriptional regulator, Crp/Fnr family, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate, ... (4 entities in total)
• 機能のキーワード: cyclic-nucleotide binding, potassium channel, lipid modulation, transport protein
• 由来する生物種: Spirochaeta thermophila
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 232018.86

構造登録者

Schmidpeter, P.A.M.,Thon, O.,Nimigean, C.M. (登録日: 2024-01-26, 公開日: 2024-09-25, 最終更新日: 2024-10-02)

主引用文献

Thon, O.,Wang, Z.,Schmidpeter, P.A.M.,Nimigean, C.M.
PIP2 inhibits pore opening of the cyclic nucleotide-gated channel SthK.
Nat Commun, 15:8230-8230, 2024

PubMed Abstract: The signaling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) regulates many ion channels. It inhibits eukaryotic cyclic nucleotide-gated (CNG) channels while activating their relatives, the hyperpolarization-activated and cyclic nucleotide-modulated (HCN) channels. The prokaryotic SthK channel from Spirochaeta thermophila shares features with CNG and HCN channels and is an established model for this channel family. Here, we show SthK activity is inhibited by PIP2. A cryo-EM structure of SthK in nanodiscs reveals a PIP2-fitting density coordinated by arginine and lysine residues from the S4 helix and the C-linker, located between voltage-sensing and pore domains of adjacent subunits. Mutation of two arginine residues weakens PIP2 inhibition with the double mutant displaying insensitivity to PIP2. We propose that PIP2 inhibits SthK by gluing S4 and S6 together, stabilizing a resting channel conformation. The PIP2 binding site is partially conserved in CNG channels suggesting the possibility of a similar inhibition mechanism in the eukaryotic homologs.

PubMed: 39300080
DOI: 10.1038/s41467-024-52469-1

実験手法

ELECTRON MICROSCOPY (2.9 Å)