Dynamic rearrangement of the outer mouth of a K+ channel during gating
Dynamic rearrangement of the outer mouth of a K+ channel during gating
复制标题
DOI：
10.1016/s0896-6273(00)80106-3
复制
发表时间：
1996-04-01
期刊：
影响因子：
16.2
通讯作者：
Yellen, G
中科院分区：
文献类型：
--
作者：
Liu, Y;Jurman, ME;Yellen, G
在长时间的刺激下，电压激活的Ki通道通过一种称为失活的门控过程关闭。这种失活门控可以通过两种不同的分子机制发生：n型，其中拴住的颗粒阻断孔的细胞内口，c型，涉及关闭外口。通过诱变在Shaker K+通道外口引入半胱氨酸残基，并通过测量化学修饰可及性的状态依赖性变化，研究了c型失活所涉及的功能运动。在c型灭活状态下，外口相邻三个残基的修饰速度比封闭状态下快130- 10000倍。在一个位置，亚基之间的状态依赖桥接或二硫交联也是可能的。这些结果给出了一个一致的画面，其中c型失活促进了局部重排和通道的收缩外口。
With prolonged stimulation, voltage-activated Ki channels close by a gating process called inactivation. This inactivation gating can occur by two distinct molecular mechanisms: N-type, in which a tethered particle blocks the intracellular mouth of the pore, and C-type, which involves a closure of the external mouth. The functional motion involved in C-type inactivation was studied by introducing cysteine residues at the outer mouth of Shaker K+ channels through mutagenesis, and by measuring state-dependent changes in accessibility to chemical modification. Modification of three adjacent residues in the outer mouth was 130-10,000-fold faster in the C-type inactivated state than in the closed state. At one position, state-dependent bridging or disulfide crosslinking between subunits was also possible. These results give a consistent picture in which C-type inactivation promotes a local rearrangement and constriction of the channel at the outer mouth.