Fast Motions of Key Methyl Groups in Amyloid-β Fibrils.
Fast Motions of Key Methyl Groups in Amyloid-β Fibrils.
复制标题
淀粉样β原纤维中关键甲基基团的快速运动。
DOI：
10.1016/j.bpj.2016.10.001
复制
发表时间：
2016
影响因子：
3.4
通讯作者：
Qiang,Wei
中科院分区：
文献类型：
--
作者：
Vugmeyster,Liliya;Ostrovsky,Dmitry;Clark,MatthewA;Falconer,IsaacB;Hoatson,GinaL;Qiang,Wei
淀粉样蛋白-β(Aβ)肽是阿尔茨海默病患者斑块的主要成分。通过对选择性氘化甲基进行固态2h NMR弛豫，我们探索了天然a β的三对称和双对称多态性以及D23N突变体原纤维的动力学。具体来说，我们研究了属于疏水核心（L17和L34）的两个亮氨酸残基的甲基，以及属于交叉β亚基之间疏水界面的M35残基，这些残基以前被发现是可水接近的。在310-140 K和两种磁场强度下进行的弛豫测量可以深入了解多晶内部和多晶之间的构象变化。单个多态性内的核心包装变化类似于对核心残基的球状蛋白所观察到的变化，而M35表现出更大程度的可变性。M35位点还显示出一个依赖于溶剂的动力学转变，其中甲基轴的较慢振幅运动在高温下被激活。以甲基轴扩散为模型的运动，其活化能是三倍多晶型的2.7倍，而D23N原纤维的活化能与三倍多晶型相似。这表明在三重晶型中疏水界面的柔韧性增强。这种差异只在水合状态下观察到，而在干燥的原纤维中不存在，突出了溶剂在腔中的作用。相反，岩心的动态行为与水合作用无关。
Amyloid-β(Aβ) peptide is the major component of plaques found in Alzheimer's disease patients. Using solid-state2H NMR relaxation performed on selectively deuterated methyl groups, we probed the dynamics in the threefold symmetric and twofold symmetric polymorphs of native Aβas well as the protofibrils of the D23N mutant. Specifically, we investigated the methyl groups of two leucine residues that belong to the hydrophobic core (L17 and L34) as well as M35 residues belonging to the hydrophobic interface between the cross-βsubunits, which has been previously found to be water-accessible. Relaxation measurements performed over 310–140 K and two magnetic field strengths provide insights into conformational variability within and between polymorphs. Core packing variations within a single polymorph are similar to what is observed for globular proteins for the core residues, whereas M35 exhibits a larger degree of variability. M35 site is also shown to undergo a solvent-dependent dynamical transition in which slower amplitude motions of methyl axes are activated at high temperature. The motions, modeled as a diffusion of methyl axis, have activation energy by a factor of 2.7 larger in the twofold compared with the threefold polymorph, whereas D23N protofibrils display a value similar to the threefold polymorph. This suggests enhanced flexibility of the hydrophobic interface in the threefold polymorph. This difference is only observed in the hydrated state and is absent in the dry fibrils, highlighting the role of solvent at the cavity. In contrast, the dynamic behavior of the core is hydration-independent.
登录
查看更多内容
影响因子：
3.8
作者：
Ringe, D;Petsko, GA
通讯作者：
Petsko, GA
氘核核磁共振揭示蛋白质甲基的玻璃态动力学。
DOI：
10.1021/jp311112j
发表时间：
2013
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Vugmeyster,Liliya;Ostrovsky,Dmitry;Penland,Kirsten;Hoatson,GinaL;Vold,RobertL
通讯作者：
Vold,RobertL
非指数 2H 自旋晶格弛豫作为玻璃态的特征
DOI：
--
发表时间：
1990
期刊：
影响因子：
--
作者：
W. Schnauss;F. Fujara;K. Hartmann;H. Sillescu
通讯作者：
H. Sillescu
影响因子：
2.7
作者：
Linser, Rasmus;Sarkar, Riddhiman;Reif, Bernd
通讯作者：
Reif, Bernd
影响因子：
15
作者：
Miller Y;Ma B;Nussinov R
通讯作者：
Nussinov R