Impact of N-terminal acetylation of α-synuclein on its random coil and lipid binding properties.
Impact of N-terminal acetylation of α-synuclein on its random coil and lipid binding properties.
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DOI：
10.1021/bi300642h
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发表时间：
2012-06-26
期刊：
影响因子：
2.9
通讯作者：
Bax A
中科院分区：
文献类型：
--
作者：
Maltsev AS;Ying J;Bax A
α-突触核蛋白（α-synuclein，aS）是一种与帕金森病病因有关的蛋白质，其N-末端乙酰化在哺乳动物中很常见。这种修改的蛋白质的结构和动力学在自由溶液中，并在其膜结合性能的影响已通过高分辨率核磁共振和圆二色性（CD）光谱进行了评估。虽然没有四聚体形式的乙酰化的aS可以被分离，N-末端乙酰化导致的化学位移扰动的前12个残基的蛋白质，从N-末端的距离逐渐减少。化学位移变化的方向和骨架3 JHH偶联的微小变化与aS前6个残基的α-螺旋度增加一致，尽管仍然存在高度的动态构象紊乱，并且螺旋结构的采样率<20%。完整蛋白质的化学位移和3 JHH数据与相应的N-末端乙酰化和非乙酰化15-残基合成肽记录的数据几乎无法区分。乙酰化肽的CD数据和表明α-螺旋特征的弱中程核Overhauser效应接触支持aS N末端α-螺旋度的增加。蛋白质的其余部分具有非常接近随机卷曲值的化学位移值，并且蛋白质的两种形式之间无法区分。在乙酰化和非乙酰化的aS之间没有观察到纤颤动力学的显着差异。然而，脂质结合特性的aS强烈影响乙酰化，并表现出独特的行为的前12个残基，指示的起始作用的N-末端残基的“起始-延伸”的过程中结合到膜。
N-Terminal acetylation of α-synuclein (aS), a protein implicated in the etiology of Parkinson’s disease, is common in mammals. The impact of this modification on the protein’s structure and dynamics in free solution and on its membrane binding properties has been evaluated by high-resolution nuclear magnetic resonance and circular dichroism (CD) spectroscopy. While no tetrameric form of acetylated aS could be isolated, N-terminal acetylation resulted in chemical shift perturbations of the first 12 residues of the protein that progressively decreased with the distance from the N-terminus. The directions of the chemical shift changes and small changes in backbone 3JHH couplings are consistent with an increase in the α-helicity of the first six residues of aS, although a high degree of dynamic conformational disorder remains and the helical structure is sampled <20% of the time. Chemical shift and 3JHH data for the intact protein are virtually indistinguishable from those recorded for the corresponding N-terminally acetylated and nonacetylated 15-residue synthetic peptides. An increase in α-helicity at the N-terminus of aS is supported by CD data on the acetylated peptide and by weak medium-range nuclear Overhauser effect contacts indicative of α-helical character. The remainder of the protein has chemical shift values that are very close to random coil values and indistinguishable between the two forms of the protein. No significant differences in the fibrillation kinetics were observed between acetylated and nonacetylated aS. However, the lipid binding properties of aS are strongly impacted by acetylation and exhibit distinct behavior for the first 12 residues, indicative of an initiation role for the N-terminal residues in an “initiation–elongation” process of binding to the membrane.
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DOI：
10.1073/pnas.0407146102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Bertoncini, CW;Jung, YS;Zweckstetter, M
通讯作者：
Zweckstetter, M
影响因子：
2.9
作者：
Bodner, Christina R.;Maltsev, Alexander S.;Dobson, Christopher M.;Bax, Ad
通讯作者：
Bax, Ad
影响因子：
3.4
作者：
Bartels, Tim;Ahlstrom, Logan S.;Beyer, Klaus
通讯作者：
Beyer, Klaus
影响因子：
2.9
作者：
Bisaglia, M;Schievano, E;Mammi, S
通讯作者：
Mammi, S
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A