Liu Pu, Huang Xuhui, Zhou Ruhong, Berne B J
Department of Chemistry, Columbia University, New York, New York 10027, USA.
Nature. 2005 Sep 1;437(7055):159-62. doi: 10.1038/nature03926.
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, resulting in the subsequent collapse of the system, as well as a depletion of water next to single surfaces. 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).
在水中蜂毒肽蛋白四聚体的自组装过程中会发生显著的水合变化。当足够大（超过1纳米²）的简单强疏水表面彼此靠近时，疏水性会在它们之间的间隙中引发干燥转变，导致系统随后坍塌，以及单个表面附近的水耗尽。在此，我们研究多结构域蛋白的疏水诱导坍塌或蛋白寡聚体的形成是否表现出类似的干燥转变。我们进行了计算机模拟来研究蜂毒肽四聚体在水中的坍塌，并观察到四聚体纳米级通道内（通道尺寸可达两到三个水分子直径）有明显的水干燥转变。这种转变虽然发生在微观长度尺度上，但类似于从液体到蒸汽的一级相变。我们发现这种干燥对三个异亮氨酸突变为疏水性较低的残基的单个突变非常敏感，并且在正确位置的此类突变可以使通道从干燥变为湿润。因此，疏水表面拓扑结构相当细微的变化会深刻影响干燥转变。我们表明，即使存在极性蛋白主链，足够疏水的蛋白表面也能诱导液 - 气转变，为进一步坍塌提供巨大驱动力。由于多结构域蛋白2,3 - 二羟基联苯双加氧酶（BphC）的坍塌中不存在干燥现象，这种行为出乎意料。
