Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Instrumentation Center, National Taiwan University, Taipei 10617, Taiwan.
Molecules. 2021 Mar 3;26(5):1346. doi: 10.3390/molecules26051346.
Cross-strand lateral ion-pairing interactions are important for antiparallel β-sheet stability. Statistical studies suggested that swapping the position of cross-strand lateral residues should not significantly affect the interaction. Herein, we swapped the position of ammonium- and carboxylate-containing residues with different side-chain lengths in a cross-strand lateral ion-pairing interaction in a β-hairpin. The peptides were analyzed by 2D-NMR. The fraction folded population and folding free energy were derived from the chemical shift data. The ion-pairing interaction energy was derived using double mutant cycle analysis. The general trends for the fraction folded population and interaction energetics remained similar upon swapping the position of the interacting charged residues. The most stabilizing cross-strand interactions were between short residues, similar to the unswapped study. However, the fraction folded populations for most of the swapped peptides were higher compared to the corresponding unswapped peptides. Furthermore, subtle differences in the ion-pairing interaction energy upon swapping were observed, most likely due to the "unleveled" relative positioning of the interacting residues created by the inherent right-handed twist of the structure. These results should be useful for developing functional peptides that rely on lateral ion-pairing interactions across antiparallel β-strands.
链间横向离子对相互作用对于反平行β-折叠的稳定性很重要。统计研究表明，交换链间横向残基的位置不应显著影响相互作用。在此，我们在β发夹中交换了具有不同侧链长度的反平行β-折叠中横向离子对相互作用的铵和羧酸残基的位置。通过二维 NMR 对肽进行分析。从化学位移数据中得出折叠分数和折叠自由能。使用双突变体循环分析得出离子对相互作用能。在交换相互作用的带电残基位置后，折叠分数和相互作用能的总体趋势仍然相似。最稳定的链间相互作用是短残基之间的相互作用，与未交换的研究相似。然而，与相应的未交换肽相比，大多数交换肽的折叠分数更高。此外，在交换时观察到离子对相互作用能的细微差异，这可能是由于结构固有的右手扭曲导致相互作用残基的相对定位“不平坦”所致。这些结果对于开发依赖于反平行β-折叠之间横向离子对相互作用的功能性肽应该是有用的。
