Biophysics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA.
Biophys J. 2011 Jun 8;100(11):2614-22. doi: 10.1016/j.bpj.2011.04.032.
How proteins evolve new functionality is an important question in biology; prestin (SLC26A5) is a case in point. Prestin drives outer hair cell somatic motility and amplifies mechanical vibrations in the mammalian cochlea. The motility of mammalian prestin is analogous to piezoelectricity, in which charge transfer is coupled to changes in membrane area occupied by the protein. Intriguingly, nonmammalian prestin orthologs function as anion exchangers but are apparently nonmotile. We previously found that mammalian prestin is sensitive to membrane thickness, suggesting that prestin's extended conformation has a thinner hydrophobic height in the lipid bilayer. Because prestin-based motility is a mammalian specialization, we initially hypothesized that nonmotile prestin orthologs, while functioning as anion transporters, should be much less sensitive to membrane thickness. We found the exact opposite to be true. Chicken prestin was the most sensitive to thickness changes, displaying the largest shift in voltage dependence. Platypus prestin displayed an intermediate response to membrane thickness and gerbil prestin was the least sensitive. To explain these observations, we present a theory where force production, rather than displacement, was selected for the evolution of prestin as a piezoelectric membrane motor.
蛋白质如何进化出新的功能是生物学中的一个重要问题； prestin（SLC26A5）就是一个很好的例子。Prestin 驱动外毛细胞的体细胞运动，并放大哺乳动物耳蜗中的机械振动。哺乳动物 prestin 的运动类似于压电性，其中电荷转移与蛋白质占据的膜面积变化耦合。有趣的是，非哺乳动物 prestin 同源物作为阴离子交换器起作用，但显然是非运动的。我们之前发现哺乳动物 prestin 对膜厚度敏感，这表明 prestin 的伸展构象在脂质双层中具有更薄的疏水性高度。由于基于 prestin 的运动是哺乳动物的特有现象，我们最初假设非运动性 prestin 同源物虽然作为阴离子转运体起作用，但对膜厚度的敏感性应该低得多。我们发现事实恰恰相反。鸡 prestin 对厚度变化最敏感，显示出电压依赖性的最大变化。鸭嘴兽 prestin 对膜厚度的反应介于中间，而沙鼠 prestin 最不敏感。为了解释这些观察结果，我们提出了一个理论，即力的产生而不是位移，被选为 prestin 作为压电膜电机的进化选择。
