Structural mechanism of C-type inactivation in K+ channels

被引:387
作者
Cuello, Luis G.
Jogini, Vishwanath
Cortes, D. Marien
Perozo, Eduardo [1 ]
机构
[1] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
关键词
SHAKER POTASSIUM CHANNELS; SELECTIVITY FILTER; SLOW INACTIVATION; ION CONDUCTION; TETRAETHYLAMMONIUM BLOCKADE; CRYSTAL-STRUCTURE; OPEN STATE; KCSA; PORE; MUTATIONS;
D O I
10.1038/nature09153
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
Interconversion between conductive and non-conductive forms of the K+ channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K+ channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 angstrom in closed KcsA (C alpha-C alpha distances at Thr 112) to 32 angstrom when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K+ channels.
引用
收藏
页码:203 / U73
页数:7
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