Observation of a dewetting transition in the collapse of the melittin tetramer
Observation of a dewetting transition in the collapse of the melittin tetramer
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DOI：
10.1038/nature03926
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发表时间：
2005-09-01
期刊：
影响因子：
64.8
通讯作者：
Berne, BJ
中科院分区：
文献类型：
--
作者：
Liu, P;Huang, XH;Berne, BJ
在蜂毒肽蛋白四聚体在水中的自组装过程中发生显著的水合变化。疏水性在简单的足够大（大于1 nm（2））的强疏水表面之间差距中诱导干燥转变，因为它们彼此接近（1-6），导致系统随后崩溃，以及单个表面旁边的水耗尽（7-10）。在这里，我们调查是否疏水诱导的多结构域蛋白质的崩溃或蛋白质寡聚体的形成表现出类似的干燥过渡。我们进行了计算机模拟，以研究蜂毒素在水中的四聚体的崩溃，并观察到一个显着的水干燥过渡内的四聚体的纳米通道（通道大小高达两个或三个水分子直径）。这种转变虽然发生在微观尺度上，但类似于从液体到蒸汽的一级相变。我们发现，这种干燥是非常敏感的单突变的三个异亮氨酸疏水性较低的残基，在正确的位置，这样的突变可以切换通道从干燥到潮湿。因此，疏水表面拓扑结构的相当微妙的变化可以深刻地影响干燥转变。我们表明，即使在存在极性蛋白质骨架的情况下，足够疏水的蛋白质表面也可以诱导液-汽转变，从而提供朝向进一步崩溃的巨大驱动力。这种行为是出乎意料的，因为在多结构域蛋白2，3-二羟基联苯双加氧酶（BphC）的塌陷中没有干燥。
Marked hydration changes occur during the self-assembly of the melittin protein tetramer in water. Hydrophobicity induces a drying transition in the gap between simple sufficiently large ( more than 1 nm(2)) strongly hydrophobic surfaces as they approach each other(1-6), resulting in the subsequent collapse of the system, as well as a depletion of water next to single surfaces(7-10). Here we investigate whether the hydrophobic induced collapse of multidomain proteins or the formation of protein oligimers exhibits a similar drying transition. We performed computer simulations to study the collapse of the tetramer of melittin in water, and observed a marked water drying transition inside a nanoscale channel of the tetramer ( with a channel size of up to two or three water-molecule diameters). This transition, although occurring on a microscopic length scale, is analogous to a first-order phase transition from liquid to vapour. We find that this drying is very sensitive to single mutations of the three isoleucines to less hydrophobic residues and that such mutations in the right locations can switch the channel from being dry to being wet. Thus, quite subtle changes in hydrophobic surface topology can profoundly influence the drying transition. We show that, even in the presence of the polar protein backbone, sufficiently hydrophobic protein surfaces can induce a liquid - vapour transition providing an enormous driving force towards further collapse. This behaviour was unexpected because of the absence of drying in the collapse of the multidomain protein 2,3-dihydroxybiphenyl dioxygenase (BphC).