Structural mechanism of C-type inactivation in K+ channels

Article

关键词: SHAKER POTASSIUM CHANNELS;    SELECTIVITY FILTER;    SLOW INACTIVATION;    ION CONDUCTION;    TETRAETHYLAMMONIUM BLOCKADE;    CRYSTAL-STRUCTURE;    OPEN STATE;    KCSA;    PORE;    MUTATIONS;   

DOI  :  10.1038/nature09153

来源: SCIE

【 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.

【 授权许可】

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