Jarvet Jüri, Danielsson Jens, Damberg Peter, Oleszczuk Marta, Gräslund Astrid
Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm 106 91, Sweden.
J Biomol NMR. 2007 Sep;39(1):63-72. doi: 10.1007/s10858-007-9176-4. Epub 2007 Jul 27.
NMR spectroscopy combined with paramagnetic relaxation agents was used to study the positioning of the 40-residue Alzheimer Amyloid beta-peptide Abeta(1-40) in SDS micelles. 5-Doxyl stearic acid incorporated into the micelle or Mn(2+) ions in the aqueous solvent were used to determine the position of the peptide relative to the micelle geometry. In SDS solvent, the two alpha-helices induced in Abeta(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 Mn(2+) 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 alpha-helix therefore resides in the SDS headgroup 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 Mn(2+), and should be buried in the hydrophobic interior of the micelle. The SDS micelles were characterized by diffusion and (15)N-relaxation measurements. Comparison of experimentally determined translational diffusion coefficients for SDS and Abeta(1-40) show that the size of SDS micelle is not significantly changed by interaction with Abeta(1-40).
核磁共振光谱结合顺磁弛豫剂被用于研究40个残基的阿尔茨海默病淀粉样β肽Abeta(1 - 40)在十二烷基硫酸钠（SDS）胶束中的定位。掺入胶束的5 - 脱氧硬脂酸或水性溶剂中的锰离子（Mn(2+)）被用于确定肽相对于胶束几何结构的位置。在SDS溶剂中，Abeta(1 - 40)中分别由15 - 24位残基和29 - 35位残基形成的两个α螺旋被柔性无结构区域包围。在Mn(2+)存在的情况下，来自这些无结构区域的核磁共振信号被强烈衰减，表明这些区域大多位于胶束外部。然而，中央螺旋（15 - 24位残基）受到5 - 脱氧硬脂酸的显著影响，不过16、20、22和23位残基受到的影响稍小。因此，这个α螺旋位于SDS头基区域，16、20、22和23位残基所在的面背离胶束的疏水内部。C端螺旋受到5 - 脱氧硬脂酸和Mn(2+)的保护，应该埋在胶束的疏水内部。通过扩散和(15)N弛豫测量对SDS胶束进行了表征。对实验测定的SDS和Abeta(1 - 40)的平移扩散系数的比较表明，SDS胶束的大小不会因与Abeta(1 - 40)的相互作用而发生显著变化。
