Characterizing Intermediates Along the Transition from Polyproline I to Polyproline II Using Ion Mobility Spectrometry-Mass Spectrometry
Characterizing Intermediates Along the Transition from Polyproline I to Polyproline II Using Ion Mobility Spectrometry-Mass Spectrometry
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DOI：
10.1021/ja505899g
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发表时间：
2014-09-10
影响因子：
15
通讯作者：
Clemmer, David E.
中科院分区：
文献类型：
--
作者：
Shi, Liuqing;Holliday, Alison E.;Clemmer, David E.
在脂肪醇中，聚脯氨酸主要以全顺式聚脯氨酸I （PPI）螺旋结构存在，而全反式聚脯氨酸II （PPII）螺旋结构在水溶液中更受欢迎。先前的离子迁移谱-质谱（IMS-MS）研究表明，聚脯氨酸的气相构象可能与溶液中相应的PPI和PPII螺旋有关[J]。理论物理。化学。[j].农业工程学报，2004,18(4):481 - 481。在这里，我们使用IMS-MS检查了与溶剂交换时从PPI螺旋到PPII螺旋的Pro13 （Pro13）转化过程相关的详细中间步骤。在不同过渡时间得到的Pro13 [M + 2H]（2+）离子的碰撞截面分布表明存在两种主要的构象，分别是PPI和PPII螺旋，以及出现在聚脯氨酸亚群中的6种构象。进一步的分析表明，过渡机制与顺序顺链异构化之后的平行过程建立PPII和两个较小的亚种群处于平衡状态。温度依赖性研究用于获得机制每一步的Arrhenius活化参数，分子动力学模拟提供了对中间体结构的深入了解。似乎脯氨酸从n端开始从顺式向反式依次翻转。然而，在最初的几个转变之后，可能的步骤发生在肽链的中心；随后，几条路径似乎同时可达。我们的研究结果反映了脯氨酸稳定亚群的存在，并为脯氨酸肽在水溶液中由PPI向PPII转化过程中的结构变化提供了新的认识
Polyproline exists predominately as the all-cis polyproline I (PPI) helix in aliphatic alcohols, whereas the all-trans polyproline II (PPII) helix is favored in aqueous solutions. Previous ion mobility spectrometry-mass spectrometry (IMS-MS) work demonstrates that the gas-phase conformations of polyproline ions can be related to the corresponding PPI and PPII helices in solution [J. Phys. Chem. B 2004, 108, 4885]. Here, we use IMS-MS to examine the detailed intermediate steps associated with the process of Polyproline-13 (Pro13) conversion from the PPI helix to the PPII helix upon solvent exchange. Collision cross section distributions of Pro13 [M + 2H](2+) ions obtained at different transition times indicate the presence of two major conformers, identified as the PPI and PPII helices, and six conformers that appear as subpopulations of polyproline. Further analysis shows a transition mechanism with sequential cistrans isomerizations followed by a parallel process to establish PPII and two smaller subpopulations at equilibrium. Temperature-dependent studies are used to obtain Arrhenius activation parameters for each step of the mechanism, and molecular dynamics simulations provide insight about the structures of the intermediates. It appears that prolines sequentially flip from cis to trans starting from the N-terminus. However, after the first few transitions, possible steps take place at the center of the peptide chain; subsequently, several pathways appear to be accessible at the same time. Our results reflect the existence of stable subpopulations in polyprolines and provide new insight into the structural changes during the transition process of polyproline peptides converting from PPI to PPII in aqueous solution