Chang G, Spencer R H, Lee A T, Barclay M T, Rees D C
Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, 147-75CH, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 1998 Dec 18;282(5397):2220-6. doi: 10.1126/science.282.5397.2220.
Mechanosensitive ion channels play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. The MscL family of large-conductance mechanosensitive channels is widely distributed among prokaryotes and may participate in the regulation of osmotic pressure changes within the cell. In an effort to better understand the structural basis for the function of these channels, the structure of the MscL homolog from Mycobacterium tuberculosis was determined by x-ray crystallography to 3.5 angstroms resolution. This channel is organized as a homopentamer, with each subunit containing two transmembrane alpha helices and a third cytoplasmic alpha helix. From the extracellular side, a water-filled opening approximately 18 angstroms in diameter leads into a pore lined with hydrophilic residues which narrows at the cytoplasmic side to an occluded hydrophobic apex that may act as the channel gate. This structure may serve as a model for other mechanosensitive channels, as well as the broader class of pentameric ligand-gated ion channels exemplified by the nicotinic acetylcholine receptor.
机械敏感离子通道在将细胞膜上的物理应力转化为电化学响应过程中发挥着关键作用。大电导机械敏感通道的MscL家族广泛分布于原核生物中，可能参与细胞内渗透压变化的调节。为了更好地理解这些通道功能的结构基础，通过X射线晶体学确定了结核分枝杆菌MscL同源物的结构，分辨率达到3.5埃。该通道由同源五聚体组成，每个亚基包含两个跨膜α螺旋和第三个胞质α螺旋。从细胞外侧看，一个直径约18埃的充满水的开口通向一个由亲水残基排列的孔道，该孔道在胞质侧变窄至一个封闭的疏水顶端，该顶端可能充当通道门。这种结构可作为其他机械敏感通道以及以烟碱型乙酰胆碱受体为代表的更广泛的五聚体配体门控离子通道类别的模型。
