6VXZ

SthK P300A cyclic nucleotide-gated potassium channel in the closed state, in complex with cAMP

6VXZ の概要

• エントリーDOI: 10.2210/pdb6vxz/pdb
• 関連するPDBエントリー: 6CJU 6VY0
• EMDBエントリー: 21453 21454 7484
• 分子名称: SthK, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate (3 entities in total)
• 機能のキーワード: transport protein
• 由来する生物種: Spirochaeta thermophila (strain ATCC 700085 / DSM 6578 / Z-1203)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 223663.15

構造登録者

Schmidpeter, P.A.M.,Rheinberger, J.,Nimigean, C.M. (登録日: 2020-02-25, 公開日: 2020-11-11, 最終更新日: 2024-03-06)

主引用文献

Schmidpeter, P.A.M.,Rheinberger, J.,Nimigean, C.M.
Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel.
Nat Commun, 11:6401-6401, 2020

PubMed Abstract: SthK, a cyclic nucleotide-modulated ion channel from Spirochaeta thermophila, activates slowly upon cAMP increase. This is reminiscent of the slow, cAMP-induced activation reported for the hyperpolarization-activated and cyclic nucleotide-gated channel HCN2 in the family of so-called pacemaker channels. Here, we investigate slow cAMP-induced activation in purified SthK channels using stopped-flow assays, mutagenesis, enzymatic catalysis and inhibition assays revealing that the cis/trans conformation of a conserved proline in the cyclic nucleotide-binding domain determines the activation kinetics of SthK. We propose that SthK exists in two forms: trans Pro300 SthK with high ligand binding affinity and fast activation, and cis Pro300 SthK with low affinity and slow activation. Following channel activation, the cis/trans equilibrium, catalyzed by prolyl isomerases, is shifted towards trans, while steady-state channel activity is unaffected. Our results reveal prolyl isomerization as a regulatory mechanism for SthK, and potentially eukaryotic HCN channels. This mechanism could contribute to electrical rhythmicity in cells.

PubMed: 33328472
DOI: 10.1038/s41467-020-20104-4

実験手法

ELECTRON MICROSCOPY (3.42 Å)