Structural models of the MscL gating mechanism.
Structural models of the MscL gating mechanism.
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DOI：
10.1016/s0006-3495(01)75751-7
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发表时间：
2001-08
影响因子：
3.4
通讯作者：
S. Sukharev;S. Durell;H. Guy
中科院分区：
文献类型：
--
作者：
S. Sukharev;S. Durell;H. Guy
结核分枝杆菌和大肠杆菌的大电导机械敏感通道 MscL 的三维结构模型被开发为闭合、中间和开放构象。建模从M的晶体结构开始。 tuberculosisMscL，每个亚基具有两个跨膜 α 螺旋 M1 和 M2 的同五聚体。前 12 个 N 末端残基在晶体结构中未解析，被建模为两亲性 α 螺旋，称为 S1。假设一束五个平行的 S1 螺旋形成细胞质门。当膜张力引起膨胀时，假设 M1 和 M2 的倾斜度随着远离孔轴而增加。假定在 S1 至 M1 连接体中增加的应力将 S1 束拉开之前发生显着扩张。在开放转变过程中，S1 螺旋和 C 末端两亲性 α 螺旋 S3 被假定平行于复合物周边的膜表面对接。所提出的门控机制揭示了 M1 和 M2 形成的可扩展跨膜桶、S1 螺旋形成的门以及连接 S1 和 M1 的“绳”之间的关键空间关系。这些模型与大量实验结果和建模标准一致。
Three-dimensional structural models of the mechanosensitive channel of large conductance, MscL, from the bacteriaMycobacterium tuberculosisandEscherichia coliwere developed for closed, intermediate, and open conformations. The modeling began with the crystal structure ofM. tuberculosisMscL, a homopentamer with two transmembraneα-helices, M1 and M2, per subunit. The first 12 N-terminal residues, not resolved in the crystal structure, were modeled as an amphipathicα-helix, called S1. A bundle of five parallel S1 helices are postulated to form a cytoplasmic gate. As membrane tension induces expansion, the tilts of M1 and M2 are postulated to increase as they move away from the axis of the pore. Substantial expansion is postulated to occur before the increased stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening transition, the S1 helices and C-terminus amphipathicα-helices, S3, are postulated to dock parallel to the membrane surface on the perimeter of the complex. The proposed gating mechanism reveals critical spatial relationships between the expandable transmembrane barrel formed by M1 and M2, the gate formed by S1 helices, and "strings" that link S1s to M1s. These models are consistent with numerous experimental results and modeling criteria.