Conformational changes of the amyloid β-peptide (1-40) adsorbed on solid surfaces
Conformational changes of the amyloid β-peptide (1-40) adsorbed on solid surfaces
复制标题
DOI：
10.1002/mabi.200400189
复制
发表时间：
2005-05-23
影响因子：
4.6
通讯作者：
Norde, W
中科院分区：
文献类型：
--
作者：
Giacomelli, CE;Norde, W
淀粉样蛋白β-肽（A β）的39-43个残基朝向β-折叠富集状态的构象变化促进肽分子的自聚集，并构成阿尔茨海默病患者中淀粉样蛋白斑的主要肽组分。A β自我聚集背后的关键问题与该肽在细胞膜上从淀粉样前体蛋白裂解后可能采取的不同途径有关。这项工作的目的是确定A β（1-40）吸附在疏水性聚四氟乙烯和亲水性二氧化硅颗粒的构象，作为模型吸附剂表面模拟非极性跨膜环境和极性，带电膜表面，分别。A β与固体表面相互作用的机制强烈依赖于颗粒的疏水/亲水特性。疏水和静电相互作用在每种情况下都有不同的贡献，导致两个表面上吸附分子的完全不同的构象变化。当肽和吸附剂之间的疏水相互作用占优势时，由于肽的非极性部分中朝向表面的H-键合，吸附的A β（1-40）主要采用α-螺旋构象。另一方面，当肽通过静电相互作用吸附时，由于吸附肽的非极性部分之间的分子间缔合，β-折叠形成被促进。无论固体吸附剂的特性如何，表面的拥挤导致吸附分子之间的分子间缔合，导致A β（1-40）的强烈聚集趋势。
The conformational change of the 39-43 residues of the amyloid beta-peptide (A beta) toward a beta-sheet enriched state promotes self-aggregation of the peptide molecules and constitutes the major peptide component of the amyloid plaques in Alzheimer patients. The crucial question behind the self-aggregation of A beta is related to the different pathways the peptide may take after cleavage from the amyloid precursor proteins at cellular membranes. This work is aiming at determining the conformation of the A beta (1-40) adsorbed on hydrophobic Teflon and hydrophilic silica particles, as model sorbent surfaces mimicking the apolar transmembrane environment and the polar, charged membrane surface, respectively. The mechanism by which the A beta interacts with solid surfaces strongly depends on the hydrophobic/hydrophilic character of the particles. Hydrophobic and electrostatic interactions contribute differently in each case, causing a completely different conformational change of the adsorbed molecules on the two surfaces. When hydrophobic interactions between the peptide and the sorbent prevail, the adsorbed A beta (1-40) mainly adopts an alpha-helix conformation due to H-bonding in the apolar part of the peptide that is oriented towards the surface. On the other hand, when the peptide adsorbs by electrostatic interactions beta-sheet formation is promoted due to intermolecular association between the apolar parts of the adsorbed peptide. Irrespective of the characteristics of the solid sorbent, crowding the sur-face results in intermolecular association between adsorbed molecules leading to a strong aggregation tendency of the A beta (1-40).