Hub Jochen S, de Groot Bert L
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1198-203. doi: 10.1073/pnas.0707662104. Epub 2008 Jan 17.
Aquaporins and aquaglyceroporins form a family of pore proteins that facilitate the efficient and selective flux of small solutes across biological membranes. We studied the selectivity of aquaporin-1 (AQP1) and the bacterial glycerol facilitator, GlpF, for O(2), CO(2), NH(3), glycerol, urea, and water. Using molecular dynamics simulations, we calculated potentials of mean force for solute permeation along the aquaporin channels and compared them with the alternative pathway across the lipid bilayer. For small solutes permeating through AQP1, a remarkable anticorrelation between permeability and solute hydrophobicity was observed, whereas the opposite trend was observed for permeation through the membrane. This finding renders AQP1 a selective filter for small polar solutes, whereas GlpF was found to be highly permeable for small solutes and permeable for larger solutes. Surprisingly, not solute-channel but water-channel interactions were found to be the key determinant underlying the selectivity mechanism of aquaporins. Hence, a hydrophobic effect, together with steric restraints, determines the selectivity of aquaporins.
水通道蛋白和水甘油通道蛋白构成了一类孔蛋白家族，它们有助于小溶质高效且选择性地穿过生物膜。我们研究了水通道蛋白1（AQP1）和细菌甘油转运蛋白GlpF对氧气、二氧化碳、氨气、甘油、尿素和水的选择性。通过分子动力学模拟，我们计算了溶质沿水通道蛋白通道渗透的平均力势，并将其与穿过脂质双层的替代途径进行了比较。对于通过AQP1渗透的小溶质，观察到渗透率与溶质疏水性之间存在显著的反相关关系，而对于穿过膜的渗透则观察到相反的趋势。这一发现使AQP1成为小极性溶质的选择性过滤器，而GlpF被发现对小溶质具有高渗透性，对较大溶质也具有渗透性。令人惊讶的是，发现决定水通道蛋白选择性机制的关键因素不是溶质-通道相互作用，而是水-通道相互作用。因此，疏水效应与空间限制共同决定了水通道蛋白的选择性。
