Zhang-Haagen Bo, Biehl Ralf, Nagel-Steger Luitgard, Radulescu Aurel, Richter Dieter, Willbold Dieter
Jülich Centre for Neutron Science & Institute of Complex Systems, Neutron Scattering (JCNS-1&ICS-1), Research Centre Jülich, Jülich, Germany.
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
PLoS One. 2016 Feb 26;11(2):e0150267. doi: 10.1371/journal.pone.0150267. eCollection 2016.
Small proteins like amyloid beta (Aβ) monomers are related to neurodegenerative disorders by aggregation to insoluble fibrils. Small angle neutron scattering (SANS) is a nondestructive method to observe the aggregation process in solution. We show that SANS is able to resolve monomers of small molecular weight like Aβ for aggregation studies. We examine Aβ monomers after prolonged storing in d-hexafluoroisopropanol (dHFIP) by using SANS and dynamic light scattering (DLS). We determined the radius of gyration from SANS as 1.0±0.1 nm for Aβ1-40 and 1.6±0.1 nm for Aβ1-42 in agreement with 3D NMR structures in similar solvents suggesting a solvent surface layer with 5% increased density. After initial dissolution in dHFIP Aβ aggregates sediment with a major component of pure monomers showing a hydrodynamic radius of 1.8±0.3 nm for Aβ1-40 and 3.2±0.4 nm for Aβ1-42 including a surface layer of dHFIP solvent molecules.
像淀粉样β蛋白（Aβ）单体这样的小蛋白质会通过聚集成不溶性纤维与神经退行性疾病相关。小角中子散射（SANS）是一种观察溶液中聚集过程的非破坏性方法。我们表明SANS能够解析像Aβ这样的小分子量单体以进行聚集研究。我们通过使用SANS和动态光散射（DLS）研究了在d-六氟异丙醇（dHFIP）中长时间储存后的Aβ单体。我们从SANS确定Aβ1-40的回转半径为1.0±0.1纳米，Aβ1-42的回转半径为1.6±0.1纳米，这与在类似溶剂中的3D NMR结构一致，表明存在密度增加5%的溶剂表面层。在最初溶解于dHFIP后，Aβ聚集体沉淀，主要成分是纯单体，Aβ1-40的流体动力学半径为1.8±0.3纳米，Aβ1-42的流体动力学半径为3.2±0.4纳米，包括dHFIP溶剂分子的表面层。
