Charge-based binding of complement component C1q to the Alzheimer amyloid beta-peptide.
Charge-based binding of complement component C1q to the Alzheimer amyloid beta-peptide.
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发表时间：
1997-05
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通讯作者：
Scott Webster;Barry Bonnell;Joseph Rogers
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作者：
Scott Webster;Barry Bonnell;Joseph Rogers
阿尔茨海默氏病经典途径的激活源自第一种蛋白质（亚成分 C1q）与淀粉样蛋白 β 肽 (Aβ) 的结合。通过竞争性酶联免疫吸附测定对 C1q 与 Aβ 的结合进行分析表明，Aβ 片段 1-16 和 1-28（而非 12-28 和 17-42）能够抑制 Aβ/C1q 相互作用，表明 Aβ1-11 区域是 C1q 结合位点。高离子强度条件也会抑制结合，这表明 A beta 1-11 区域中的带电侧链对于 A beta/c1q 相互作用至关重要。结合的超微结构证据由铂复制品电子显微镜提供。连同之前将 C1q A 链的 14-26 区域作为 A beta 结合位点的论证一起，这些发现表明 A beta 1-11 中的负电荷簇和 C1qA14-26 中的正电荷簇之间的吸引力介导了 A beta 和 C1q 的结合。
Activation of the classical pathway in Alzheimer's disease derives from the binding of the first protein, subcomponent C1q, to the amyloid beta-peptide (A beta). Analysis of the binding of C1q to A beta by competitive enzyme-linked immunosorbent assay shows that A beta fragments 1-16 and 1-28 but not 12-28 and 17-42 are capable of inhibiting the A beta/C1q interaction, implicating the A beta 1-11 region as the C1q binding site. Binding is also shown to be inhibited by conditions of high ionic strength, suggesting that charged side chains in the A beta 1-11 region are critical to the A beta/c1q interaction. Ultrastructural evidence of binding is provided by platinum replica electron microscopy. Along with a previous demonstration of the 14-26 region of the C1q A chain as the A beta binding site, these findings suggest that attractions between a negative charge cluster in A beta 1-11 and a positive charge cluster in C1qA14-26 mediate the binding of A beta and C1q.