Bilayer-Mediated Structural Transitions Control Mechanosensitivity of the TREK-2 K2P Channel.

ABSTRACT: The mechanosensitive two-pore domain (K2P) K⁺ channels (TREK-1, TREK-2, and TRAAK) are important for mechanical and thermal nociception. However, the mechanisms underlying their gating by membrane stretch remain controversial. Here we use molecular dynamics simulations to examine their behavior in a lipid bilayer. We show that TREK-2 moves from the "down" to "up" conformation in direct response to membrane stretch, and examine the role of the transmembrane pressure profile in this process. Furthermore, we show how state-dependent interactions with lipids affect the movement of TREK-2, and how stretch influences both the inner pore and selectivity filter. Finally, we present functional studies that demonstrate why direct pore block by lipid tails does not represent the principal

SUBMITTER: Aryal P 

PROVIDER: S-EPMC5415359 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature