Tropsha A, Bowen J P, Brown F K, Kizer J S
Brain and Development Research Center, University of North Carolina, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9488-92. doi: 10.1073/pnas.88.21.9488.
The leucine zipper proteins are a group of transcriptional regulators that dimerize to form a DNA binding domain. It has been proposed that this dimerization results from the hydrophobic association of the alpha-helices of two leucine zipper monomers into a coiled coil. We propose a model for a coiled coil based on a periodic hydrophobic-hydrophilic amino acid motif found in the leucine zipper regions of 11 transcriptional regulatory proteins. This model predicts the symmetrical formation of secondary hydrogen bonds between the polar side chains of one helix and the peptide carbonyls of the opposite chain, supplementing the interactions between hydrophobic side chains. Physical modeling (CPK) and in vacuo molecular mechanics calculations of the stability of the GCN4 leucine zipper coiled coil configured in accordance with this model demonstrate a greater stability for this conformer than for a conformer configured according to a current hydrophobic model. Molecular dynamics simulations show similar stability of the two models in vacuo but a higher stability of the hydrophobic model in water.
亮氨酸拉链蛋白是一组转录调节因子，它们二聚化形成一个DNA结合结构域。有人提出，这种二聚化是由两个亮氨酸拉链单体的α螺旋通过疏水作用缔合形成卷曲螺旋所致。我们基于在11种转录调节蛋白的亮氨酸拉链区域中发现的周期性疏水-亲水氨基酸基序，提出了一个卷曲螺旋模型。该模型预测，一个螺旋的极性侧链与相对链的肽羰基之间会对称形成二级氢键，从而补充疏水侧链之间的相互作用。根据该模型构建的GCN4亮氨酸拉链卷曲螺旋的物理模型（CPK）和真空中分子力学稳定性计算表明，这种构象异构体比根据当前疏水模型构建的构象异构体具有更高的稳定性。分子动力学模拟表明，两种模型在真空中具有相似的稳定性，但疏水模型在水中具有更高的稳定性。
