Structural differences between Abeta(1-40) intermediate oligomers and fibrils elucidated by proteolytic fragmentation and hydrogen/deuterium exchange.
Structural differences between Abeta(1-40) intermediate oligomers and fibrils elucidated by proteolytic fragmentation and hydrogen/deuterium exchange.
复制标题
通过蛋白水解断裂和氢/氘交换阐明 Abeta(1-40) 中间寡聚物和原纤维之间的结构差异。
DOI：
10.1016/j.bpj.2008.10.022
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发表时间：
2009
影响因子：
3.4
通讯作者：
Fernandez,ErikJ
中科院分区：
文献类型：
--
作者：
Zhang,Aming;Qi,Wei;Good,TheresaA;Fernandez,ErikJ
The aggregation of amyloid-βprotein (Aβ) in vivo is a critical pathological event in Alzheimer's disease. Although more and more evidence shows that the intermediate oligomers are the primary neurotoxic species in Alzheimer's disease, the particular structural features responsible for the toxicity of these intermediates are poorly understood. We measured the peptide level solvent accessibility of multiple Aβ(1-40) aggregated states using hydrogen exchange detected by mass spectrometry. A gradual reduction in solvent accessibility, spreading from the C-terminal region to the N-terminal region was observed with ever more aggregated states of Aβpeptide. The observed hydrogen exchange protection begins with reporter peptides 20-34 and 35-40 in low molecular weight oligomers found in fresh samples and culminates with increasing solvent protection of reporter peptide 1-16 in long time aged fibrillar species. The more solvent exposed structure of intermediate oligomers in the N-termini relative to well-developed fibrils provides a novel explanation for the structure-dependent neurotoxicity of soluble oligomers reported previously.
