Accurate determination of interstrand distances and alignment in amyloid fibrils by magic angle spinning NMR.
Accurate determination of interstrand distances and alignment in amyloid fibrils by magic angle spinning NMR.
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DOI：
10.1021/jp106675h
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发表时间：
2010-10-28
影响因子：
3.3
通讯作者：
Griffin, Robert G.
中科院分区：
文献类型：
--
作者：
Caporini, Marc A.;Bajaj, Vikram S.;Veshtort, Mikhail;Fitzpatrick, Anthony;MacPhee, Cait E.;Vendruscolo, Michele;Dobson, Christopher M.;Griffin, Robert G.
淀粉样原纤维是结构有序的蛋白质聚集体，其形成与许多神经退行性疾病和其他疾病相关。由于这个原因，它们的高分辨率结构是相当感兴趣的，并已使用广泛的技术进行了研究，特别是电子显微镜，X射线衍射和魔角旋转（MAS）NMR。由于光谱中的优异分辨率，MAS NMR独特地能够提供关于淀粉样蛋白结构的所有水平的位点特异性原子分辨率信息：（1）单体，其包装成几个（2）原丝，这些原丝继而缔合形成（3）原纤维。基于我们的甲状腺素运载蛋白（TTR 105 -115）的淀粉样蛋白形成肽单体的高分辨率结构，我们在肽中的7个不同位点引入单个1- 13 C标记的氨基酸，并测量分子间羰基-羰基距离，精度为~0.11 A。我们的研究结果最终建立了一个平行的，在寄存器中，拓扑结构的这种肽包装成一个β-折叠，并提供了必要的约束条件的原纤维的原子分辨率结构的测定。此外，我们采用的方法，结合的双量子过滤变种的绘图再耦合序列和多自旋数值模拟SPINEVOLUTION的基础上，是一般的，应该适用于广泛的系统。
Amyloid fibrils are structurally ordered aggregates of proteins whose formation is associated with many neurodegenerative and other diseases. For that reason, their high resolution structures are of considerable interest and have been studied using a wide range of techniques, notably electron microscopy, x-ray diffraction, and magic angle spinning (MAS) NMR. Because of the excellent resolution in the spectra, MAS NMR is uniquely capable of delivering site-specific, atomic resolution information about all levels of amyloid structure: (1) the monomer, which packs into several (2) protofilaments that in turn associate to form a (3) fibril. Building upon our high resolution structure of the monomer of an amyloid-forming peptide from transthyretin (TTR105-115), we introduce single 1-13C labeled amino acids at seven different sites in the peptide and measure intermolecular carbonyl-carbonyl distances with an accuracy of ~0.11 A. Our results conclusively establish a parallel, in register, topology for the packing of this peptide into a β-sheet and provide constraints essential for the determination of an atomic resolution structure of the fibril. Furthermore, the approach we employ, based on a combination of a double-quantum filtered variant of the DRAWS recoupling sequence and multispin numerical simulations in SPINEVOLUTION, is general and should be applicable to a wide range of systems.
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影响因子：
2.8
作者：
Carravetta, M;Edén, M;Levitt, MH
通讯作者：
Levitt, MH
影响因子：
4.4
作者：
BENNETT, AE;RIENSTRA, CM;GRIFFIN, RG
通讯作者：
GRIFFIN, RG
DOI：
10.1073/pnas.0900908106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Bajaj, Vikram S.;Mak-Jurkauskas, Melody L.;Griffin, Robert G.
通讯作者：
Griffin, Robert G.
影响因子：
2.2
作者：
Costa, PR;Sun, BQ;Griffin, RG
通讯作者：
Griffin, RG
影响因子：
4.4
作者：
Bennett, AE;Rienstra, CM;Griffin, RG
通讯作者：
Griffin, RG