Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Science. 2012 Jan 27;335(6067):436-41. doi: 10.1126/science.1213808.
TRAAK channels, members of the two-pore domain K(+) (potassium ion) channel family K2P, are expressed almost exclusively in the nervous system and control the resting membrane potential. Their gating is sensitive to polyunsaturated fatty acids, mechanical deformation of the membrane, and temperature changes. Physiologically, these channels appear to control the noxious input threshold for temperature and pressure sensitivity in dorsal root ganglia neurons. We present the crystal structure of human TRAAK at a resolution of 3.8 angstroms. The channel comprises two protomers, each containing two distinct pore domains, which create a two-fold symmetric K(+) channel. The extracellular surface features a helical cap, 35 angstroms tall, that creates a bifurcated pore entryway and accounts for the insensitivity of two-pore domain K(+) channels to inhibitory toxins. Two diagonally opposed gate-forming inner helices form membrane-interacting structures that may underlie this channel's sensitivity to chemical and mechanical properties of the cell membrane.
TRAAK 通道是双孔域钾 (K+) (钾离子) 通道家族 K2P 的成员，几乎只在神经系统中表达，控制静息膜电位。它们的门控对多不饱和脂肪酸、膜的机械变形和温度变化敏感。在生理上，这些通道似乎控制着背根神经节神经元对温度和压力敏感性的有害输入阈值。我们展示了分辨率为 3.8 埃的人类 TRAAK 的晶体结构。该通道由两个亚基组成，每个亚基包含两个不同的孔域，形成一个二倍对称的 K(+) 通道。细胞外表面有一个 35 埃高的螺旋帽，形成一个分叉的孔入口，这解释了双孔域 K(+) 通道对抑制性毒素不敏感的原因。两个对角相对的门控形成内螺旋，形成与细胞膜相互作用的结构，这可能是该通道对细胞膜化学和机械特性敏感的基础。
