Intermolecular alignment in Y145Stop human prion protein amyloid fibrils probed by solid-state NMR spectroscopy.
Intermolecular alignment in Y145Stop human prion protein amyloid fibrils probed by solid-state NMR spectroscopy.
复制标题
DOI：
10.1021/ja206469q
复制
发表时间：
2011-09-07
影响因子：
15
通讯作者：
Jaroniec, Christopher P.
中科院分区：
文献类型：
--
作者：
Helmus, Jonathan J.;Surewicz, Krystyna;Apostol, Marcin I.;Surewicz, Witold K.;Jaroniec, Christopher P.
人朊蛋白的Y145 Stop突变体huPrP 23 -144与PrP脑淀粉样血管病（一种遗传性淀粉样疾病）有关，也是研究淀粉样蛋白菌株分子基础的有价值的体外模型。先前通过魔角旋转（MAS）固态NMR对huPrP 23 -144淀粉样蛋白的研究揭示了C末端附近的致密的富含β的淀粉样蛋白核心区域和非结构化的N末端结构域。在这里，重点是理解huPrP 23 -144原纤维的高级结构，我们使用MAS NMR技术和由15 N标记的蛋白质和用[1，3 - 13 C]或[2- 13 C]甘油制备的13 C-huPrP 23 -144的等摩尔混合物形成的原纤维探测淀粉样蛋白核心内β链的分子间排列。在2D 15 N-13 C光谱中观察到的涉及骨架原子的许多分子间相关性明确地表明β-折叠核心的整体平行配准排列。报告分子间15 N-13 CO和15 N-13 C α偶极偶联的其他实验得出的估计链间距在平行β折叠典型距离约4.7-4.8 μ m的约10%范围内。
The Y145Stop mutant of human prion protein, huPrP23-144, has been linked to PrP cerebral amyloid angiopathy, an inherited amyloid disease, and also serves as a valuable in vitro model for investigating the molecular basis of amyloid strains. Prior studies of huPrP23-144 amyloid by magic-angle spinning (MAS) solid-state NMR revealed a compact β-rich amyloid core region near the C-terminus and an unstructured N-terminal domain. Here, with the focus on understanding the higher order architecture of huPrP23-144 fibrils, we probe the intermolecular alignment of β-strands within the amyloid core using MAS NMR techniques and fibrils formed from equimolar mixtures of 15N-labeled protein and 13C-huPrP23-144 prepared with [1,3-13C] or [2-13C]glycerol. Numerous intermolecular correlations involving backbone atoms observed in 2D 15N-13C spectra unequivocally suggest an overall parallel in-register alignment of the β-sheet core. Additional experiments that report on intermolecular 15N-13CO and 15N-13Cα dipolar couplings yield an estimated strand spacing that is within ~10% of the ~4.7–4.8 Å distances typical for parallel β-sheets.
登录
查看更多内容
影响因子：
3.3
作者：
Caporini, Marc A.;Bajaj, Vikram S.;Veshtort, Mikhail;Fitzpatrick, Anthony;MacPhee, Cait E.;Vendruscolo, Michele;Dobson, Christopher M.;Griffin, Robert G.
通讯作者：
Griffin, Robert G.
DOI：
10.1073/pnas.262663499
发表时间：
2002-12-24
影响因子：
11.1
作者：
Petkova, AT;Ishii, Y;Tycko, R
通讯作者：
Tycko, R
影响因子：
4.4
作者：
Nieuwkoop, Andrew J.;Wylie, Benjamin J.;Rienstra, Chad M.
通讯作者：
Rienstra, Chad M.
DOI：
10.1073/pnas.0706522104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Cobb, Nathan J.;Soennichsen, Frank D.;Surewicz, Witold K.
通讯作者：
Surewicz, Witold K.
影响因子：
15
作者：
Madine, Jillian;Jack, Edward;Middleton, David A.
通讯作者：
Middleton, David A.