Crystal Structure of the Human K2P TRAAK, a Lipid- and Mechano-Sensitive K+ Ion Channel

被引:322
作者
Brohawn, Stephen G.
del Marmol, Josefina
MacKinnon, Roderick [1 ]
机构
[1] Rockefeller Univ, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA
关键词
POLYUNSATURATED FATTY-ACIDS; DOMAIN POTASSIUM CHANNELS; ARACHIDONIC-ACID; TREK-1; PORE; RESOLUTION; TANDEM; LOCALIZATION; ACTIVATION; EXPRESSION;
D O I
10.1126/science.1213808
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:436 / 441
页数:6
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