1.A.1.9.3
Neuronal 2-P (4 TMS) domain K⁺ membrane tension-gated channel, TRAAK (stimulated by arachidonic acid and polyunsaturated fatty acids (Fink et al., 1998). The crystal structures of conductive and nonconductive human K2P TRAAK K⁺ channel has been solved (Brohawn et al., 2012; Brohawn et al. 2014). Regulated by mechanical deformation of the membrane and temperature as well as polyunsaturated fatty acids (Brohawn et al., 2012). Multiple modalities converge on a common gate to control K2P channel function (Bagriantsev et al., 2011).  In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Å-wide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of transmembrane helix 4 about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures provodes a biophysical explanation for TRAAK mechanosensitivity--an expansion in cross-sectional area up to 2.7 nm² in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation (Brohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the clBrohawn et al. 2014). Regulated by mechanical deformation of the membrane and temperature as well as polyunsaturated fatty acids (Brohawn et al., 2012). Multiple modalities converge on a common gate to control K2P channel function (Bagriantsev et al., 2011).  In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Å-wide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of transmembrane helix 4 about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures provodes a biophysical explanation for TRAAK mechanosensitivity--an expansion in cross-sectional area up to 2.7 nm² in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation (Brohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the clBrohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the closed state (Rasmussen 2016).