Armstrong Craig T, Mason Philip E, Anderson J L Ross, Dempsey Christopher E
School of Biochemistry, Bristol University, Bristol BS8 1TD, UK.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems, 16610 Prague 6, Czech Republic.
Sci Rep. 2016 Feb 22;6:21759. doi: 10.1038/srep21759.
Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.
电压敏感离子通道和酶的电压感应结构域（VSD）中的门控电荷由精氨酸侧链而非赖氨酸携带。分子动力学模拟表明，这种对精氨酸的偏好可能源于侧链胍基独特的水合特性，该特性有助于其穿过封闭VSD中心的疏水塞。为了测试该模型中隐含的侧链相互作用，我们检查了蛋白质数据库中蛋白质里精氨酸和赖氨酸的侧链与19种非甘氨酸氨基酸各自的相互作用。精氨酸胍基与胍基平面上方和下方的非极性芳香族和脂肪族侧链相互作用，而与极性侧链的氢键作用则限于平面内位置。相比之下，非极性侧链主要与赖氨酸侧链的脂肪族部分相互作用。正如在蛋白质结构和分子动力学模拟中所观察到的，精氨酸和赖氨酸的水合特性在它们与非极性和极性侧链各自的相互作用中得到强烈体现，并且这可能是VSD中偏好精氨酸作为可移动电荷载体的基础。
