ALAMETHICIN - A RICH MODEL FOR CHANNEL BEHAVIOR
ALAMETHICIN - A RICH MODEL FOR CHANNEL BEHAVIOR
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DOI：
10.1016/s0006-3495(84)84151-x
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发表时间：
1984-01-01
影响因子：
3.4
通讯作者：
MARSHALL, GR
中科院分区：
文献类型：
--
作者：
HALL, JE;VODYANOY, I;MARSHALL, GR
丙甲霉素是一种由20个氨基酸组成的肽，作为电压门控通道的模型已经研究了许多年。最近，已公开了丙甲霉素晶体的X射线结构和NMR溶液结构（Fox和理查兹，1982. Bannerjee等人，1983年）。这两种结构表明，分子的氨基末端形成一个稳定的α-螺旋9或10个残基的长度和COOH-末端表现出可变的氢键模式。我们已经使用合成类似物的丙甲霉素，以测试其作用模式的各种假设。作为这些研究的结果，我们提出了一种通道结构，其中COOH-末端残基结合在一起作为β-桶，使α-螺旋在电场的影响下自由旋转并门控通道。虽然每个通道的单体数量随实验条件而变化，但每个单体的门控电荷保持接近于从α-螺旋门预期的电荷。我们还可以通过改变丙甲霉素类似物上的电荷来改变开启通道的电压的符号。通道总是轻微的阳离子选择性，即使形成的单体负，正，或零形式电荷。通道在低离子强度溶液中比在高离子强度溶液中更不稳定。最后，丙甲霉素电导参数随膜厚度的变化而系统地变化。我们展示了如何这些结果和其他文献中可以解释一个相当详细的结构模型。该模型可以很容易地推广到更适合于高分子量单肽链蛋白质的形式。
Alamethicin, a 20-amino acid peptide, has been studied for a number of years as a model for voltage-gated channels. Recently both the x-ray structure of alamethicin in crystal and an NMR solution structure have been published (Fox and Richards, 1982. Bannerjee et al., 1983). Both structures show that the amino end of the molecule forms a stable alpha-helix nine or 10 residues in length and that the COOH-terminal ends exhibits a variable hydrogen bonding pattern. We have used synthetic analogues of alamethicin to test various hypotheses of its mode of action. As a result of these studies we propose a channel structure in which the COOH-terminal residues bond together as a beta-barrel, leaving the alpha- helices free to rotate under the influence of the electric field and gate the channel. Though the number of monomers per channel varies with experimental conditions, the gating charge per monomer stays close to that expected from an alpha-helical gate. We can also alter the sign of the voltage which turns on a channel by varying the charge on the alamethicin analogue. Channels are always slightly cation-selective even though formed by monomers with negative, positive, or zero formal charge. Channels are less stable in low ionic strength solutions than high. Finally, alamethicin conductance parameters vary systematically with changes in membrane thickness. We show how these results and others in the literature can be explained by a fairly detailed structural model. The model can be easily generalized to a form more suited to high molecular weight single-peptide-chain proteins.