Positioning of the Alzheimer Aβ(1-40) peptide in SDS micelles using NMR and paramagnetic probes
Positioning of the Alzheimer Aβ(1-40) peptide in SDS micelles using NMR and paramagnetic probes
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DOI：
10.1007/s10858-007-9176-4
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Graeslund, Astrid
中科院分区：
文献类型：
--
作者：
Jarvet, Jueri;Danielsson, Jens;Graeslund, Astrid
NMR光谱结合顺磁弛豫剂用于研究40个残基的阿尔茨海默淀粉样蛋白β-肽A β（1-40）在SDS胶束中的定位。5-Doxyl硬脂酸纳入胶束或Mn 2+离子在水性溶剂中被用来确定相对于胶束几何形状的肽的位置。在SDS溶剂中，在A β（1-40）中诱导的两个α-螺旋（分别包含残基15-24和29-35）被柔性非结构化区域包围。来自这些非结构化区域的NMR信号在Mn 2+的存在下强烈衰减，表明这些区域主要位于胶束外部。中心螺旋（残基15-24）受到5-doxyl硬脂酸的显著影响，但对残基16、20、22和23的影响较小。因此，该α-螺旋存在于SDS头基区域中，其中具有残基16、20、22和23的面远离胶束的疏水内部。C-末端螺旋受到5-doxyl硬脂酸和Mn 2+的保护，并且应该被埋在胶束的疏水内部。SDS胶束的特征在于扩散和N-15-松弛测量。实验测定的SDS和A β（1-40）的平移扩散系数的比较表明，SDS胶束的大小没有显着改变与A β（1-40）的相互作用。
NMR spectroscopy combined with paramagnetic relaxation agents was used to study the positioning of the 40-residue Alzheimer Amyloid beta-peptide A beta(1-40) in SDS micelles. 5-Doxyl stearic acid incorporated into the micelle or Mn2+ ions in the aqueous solvent were used to determine the position of the peptide relative to the micelle geometry. In SDS solvent, the two a-helices induced in A beta(1-40), comprising residues 15-24, and 29-35, respectively, are surrounded by flexible unstructured regions. NMR signals from these unstructured regions are strongly attenuated in the presence of Mn2+ showing that these regions are positioned mostly outside the micelle. The central helix (residues 15-24) is significantly affected by 5-doxyl stearic acid however somewhat less for residues 16, 20, 22 and 23. This a-helix therefore resides in the SDS head-group region with the face with residues 16, 20, 22 and 23 directed away from the hydrophobic interior of the micelle. The C-terminal helix is protected both from 5-doxyl stearic acid and Mn2+, and should be buried in the hydrophobic interior of the micelle. The SDS micelles were characterized by diffusion and N-15-relaxation measurements. Comparison of experimentally determined translational diffusion coefficients for SDS and A beta(1-40) show that the size of SDS micelle is not significantly changed by interaction with A beta(1-40).