Biophys J. 2010 Oct 6;99(7):L56-8. doi: 10.1016/j.bpj.2010.08.055.
It is well accepted that cotransporters facilitate water movement by two independent mechanisms: osmotic flow through a water channel in the protein and flow driven by ion/substrate cotransport. However, the molecular mechanism of transport-linked water flow is controversial. Some researchers believe that it occurs via cotransport, in which water is pumped along with the transported cargo, while others believe that flow is osmotic in response to an increase in intracellular osmolarity. In this letter, we report the results of a 200-ns molecular dynamics simulation of the sodium-dependent galactose cotransporter vSGLT. Our simulation shows that a significant number of water molecules cross the protein through the sugar-binding site in the presence as well as the absence of galactose, and 70-80 water molecules accompany galactose as it moves from the binding site into the intracellular space. During this event, the majority of water molecules in the pathway are unable to diffuse around the galactose, resulting in water in the inner half of the transporter being pushed into the intracellular space and replaced by extracellular water. Thus, our simulation supports the notion that cotransporters act as both passive water channels and active water pumps with the transported substrate acting as a piston to rectify the motion of water.
人们普遍认为，协同转运蛋白通过两种独立的机制促进水的运动：蛋白质中的水通道的渗透流和离子/底物协同转运驱动的流。然而，运输相关的水流动的分子机制仍存在争议。一些研究人员认为它是通过协同转运发生的，在协同转运中，水与被转运的货物一起被泵入，而另一些人则认为流动是渗透的，是对细胞内渗透压增加的响应。在这封信中，我们报告了对依赖于钠的半乳糖协同转运蛋白 vSGLT 进行 200 纳秒分子动力学模拟的结果。我们的模拟表明，在有和没有半乳糖的情况下，大量水分子通过糖结合位点穿过蛋白质，并且在半乳糖从结合位点移动到细胞内空间时，有 70-80 个水分子伴随其移动。在这个过程中，途径中的大多数水分子无法在半乳糖周围扩散，导致转运蛋白内部的水分子被推入细胞内空间，被细胞外的水取代。因此，我们的模拟支持了这样的观点，即协同转运蛋白既是被动的水通道，也是主动的水泵，被转运的底物作为活塞来纠正水的运动。
