Interpeptide interactions induce helix to strand structural transition in Abeta peptides.
Interpeptide interactions induce helix to strand structural transition in Abeta peptides.
复制标题
肽间相互作用诱导 Abeta 肽中螺旋到链的结构转变。
DOI：
10.1002/prot.22406
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发表时间：
2009
期刊：
影响因子：
2.9
通讯作者：
Klimov,DmitriK
中科院分区：
文献类型：
--
作者：
Takeda,Takako;Klimov,DmitriK
使用双交换分子动力学和全原子隐式溶剂模型计算与淀粉样蛋白纤维边缘结合的Aβ单体、二聚体和Aβ肽的结构倾向。这些系统大致代表了Aβ聚集的不同阶段。Aβ单体显示在N末端（残基13至21）形成螺旋结构。Aβ二聚体中的肽间相互作用，特别是与原纤维结合的肽间相互作用，诱导二级结构发生显著变化，从螺旋状态向β链构象转变。Aβ肽的10-23区是聚集时肽间相互作用的主要区域。通过比较模拟计算的Aβ单体的化学位移和实验获得的化学位移来测试模拟结果。我们的模拟设计抗聚集的Aβ变体的可能影响进行了讨论。Proteins 2009.© 2009 Wiley‐利斯公司
Replica exchange molecular dynamics and all‐atom implicit solvent model are used to compute the structural propensities in Aβ monomers, dimers, and Aβ peptides bound to the edge of amyloid fibril. These systems represent, on an approximate level, different stages in Aβ aggregation. Aβ monomers are shown to form helical structure in the N‐terminal (residues 13 to 21). Interpeptide interactions in Aβ dimers and, especially, in the peptides bound to the fibril induce a dramatic shift in the secondary structure, from helical states toward β‐strand conformations. The sequence region 10–23 in Aβ peptide is found to form most of interpeptide interactions upon aggregation. Simulation results are tested by comparing the chemical shifts in Aβ monomers computed from simulations and obtained experimentally. Possible implications of our simulations for designing aggregation‐resistant variants of Aβ are discussed. Proteins 2009. © 2009 Wiley‐Liss, Inc.