Vaden Timothy D, Gowers Sally A N, Snoek Lavina C
Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
J Am Chem Soc. 2009 Feb 25;131(7):2472-4. doi: 10.1021/ja807760d.
In Alzheimer's disease, the tau protein forms intracellular amyloid fibrils in which the (306)VQIVYK(311) sequence adopts parallel beta-sheets, enabling fibril formation via cross-beta "steric zippers". We investigated aggregation of the protected segment (Ac-VQIVYK-NHMe) using IR/UV hole-burning spectroscopy in the NH stretch region in a cold molecular beam combined with DFT calculations in order to characterize its structure and identify the noncovalent interactions generally responsible for aggregation and stabilization in amyloid peptides. The computed and experimental IR spectra suggest that the tau-protein fragments form extended beta-strands that are combined in a beta-sheet through characteristic backbone hydrogen bonds, indicating that this secondary structure is energetically most attractive and readily forms in the gas phase, without any "guiding" interactions from a solvent or protein environment.
在阿尔茨海默病中，tau蛋白形成细胞内淀粉样原纤维，其中(306)VQIVYK(311)序列采用平行β-折叠，通过交叉β“空间拉链”实现原纤维形成。我们使用红外/紫外空穴烧蚀光谱法在冷分子束的NH伸缩区域研究了受保护片段(Ac-VQIVYK-NHMe)的聚集，并结合密度泛函理论计算，以表征其结构并确定通常负责淀粉样肽聚集和稳定的非共价相互作用。计算得到的和实验测得的红外光谱表明，tau蛋白片段形成延伸的β-链，这些β-链通过特征性的主链氢键结合在β-折叠中，这表明这种二级结构在能量上最具吸引力，并且在气相中很容易形成，无需来自溶剂或蛋白质环境的任何“引导”相互作用。
