Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel
Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel
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DOI：
10.1038/nsmb895
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发表时间：
2005-02-01
影响因子：
16.8
通讯作者：
Booth, IR
中科院分区：
文献类型：
--
作者：
Edwards, MD;Li, YZ;Booth, IR
最近解决了大肠杆菌MscS机械敏感通道的开放形式的晶体结构。然而，封闭状态和门控转变的构象仍然没有表征。孔衬跨膜螺旋含有保守的富含甘氨酸和丙氨酸的基序，其形成螺旋-螺旋界面。我们表明，引入'旋钮'上的光滑甘氨酸面取代甘氨酸与丙氨酸，并取代保守的丙氨酸与较大的残基，增加门控所需的压力。甘氨酸-甘氨酸界面的产生降低了活化压力。残基Gly 104，Ala 106和Gly 108，侧翼的疏水密封的重要性，证明。提出了一种新的结构模型，包括旋转和倾斜的孔衬螺旋的封闭到开放的过渡。在Ala 106处引入甘氨酸通过作为Gly 104和Gly 108处突变所见缺陷的有力抑制剂来验证该模型。
The crystal structure of an open form of the Escherichia coli MscS mechanosensitive channel was recently solved. However, the conformation of the closed state and the gating transition remain uncharacterized. The pore-lining transmembrane helix contains a conserved glycine- and alanine-rich motif that forms a helix-helix interface. We show that introducing `knobs' on the smooth glycine face by replacing glycine with alanine, and substituting conserved alanines with larger residues, increases the pressure required for gating. Creation of a glycine- glycine interface lowers activation pressure. The importance of residues Gly104, Ala106 and Gly108, which flank the hydrophobic seal, is demonstrated. A new structural model is proposed for the closed-to-open transition that involves rotation and tilt of the pore-lining helices. Introduction of glycine at Ala106 validated this model by acting as a powerful suppressor of defects seen with mutations at Gly104 and Gly108.