One pocket to activate them all (?): Efforts on understanding the modulator pocket in K2P channels.

ABSTRACT: The modulator pocket is a cryptic site discovered in the TREK1 (K_2P2.1) K2P channel. This pocket, located close to the selectivity filter, accommodates agonists that enhance the channel's activity. Since its discovery, equivalent sites in other K2P channels have been shown to bind various ligands, both endogenous and exogenous. In this review, we attempt to elucidate how the modulator pocket contributes to K2P channel activation. To this end, we first describe the gating mechanisms reported in the literature and rationalize their modes of action. We then highlight previous experimental and computational evidence for agonists that bind to the modulator pocket, together with mutations at this site that affect gating. Finally, we elaborate how the activation signal arising from the

SUBMITTER: Mendez-Otalvaro E 

PROVIDER: S-EPMC12758241 | biostudies-literature | 2026 Dec

REPOSITORIES: biostudies-literature