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首页> 外文期刊>Scientific reports. >Presence of intrinsically disordered proteins can inhibit the nucleation phase of amyloid fibril formation of Aβ(1–42) in amino acid sequence independent manner
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Presence of intrinsically disordered proteins can inhibit the nucleation phase of amyloid fibril formation of Aβ(1–42) in amino acid sequence independent manner

机译：本质上无序的蛋白质的存在可以抑制氨基酸序列独立方式中Aβ（1-42）的淀粉样蛋白原纤维形成的成核阶段

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The molecular shield effect was studied for intrinsically disordered proteins (IDPs) that do not adopt compact and stable protein folds. IDPs are found among many stress-responsive gene products and cryoprotective- and drought-protective proteins. We recently reported that some fragments of human genome-derived IDPs are cryoprotective for cellular enzymes, despite a lack of relevant amino acid sequence motifs. This sequence-independent IDP function may reflect their molecular shield effect. This study examined the inhibitory activity of IDPs against fibril formation in an amyloid beta peptide (Aβ(1–42)) model system. Four of five human genome-derived IDPs (size range 20 to 44 amino acids) showed concentration-dependent inhibition of amyloid formation (IC50 range between 60 and 130?μM against 20?μM Aβ(1–42)). The IC50 value was two orders of magnitude lower than that of polyethylene-glycol and dextran, used as neutral hydrophilic polymer controls. Nuclear magnetic resonance with 15?N-labeled Aβ(1–42) revealed no relevant molecular interactions between Aβ(1–42) and IDPs. The inhibitory activities were abolished by adding external amyloid-formation seeds. Therefore, IDPs seemed to act only at the amyloid nucleation phase but not at the elongation phase. These results suggest that IDPs (0.1?mM or less) have a molecular shield effect that prevents aggregation of susceptible molecules.
机译：研究了分子屏蔽效应，用于本型蛋白质（IDP），不采用紧凑且稳定的蛋白质折叠。在许多应激响应基因产品和冷冻保护和干旱保护蛋白中发现了IDP。尽管缺乏相关的氨基酸序列基序，我们最近报道了对细胞酶的一些人类基因组衍生的IDPS的一些碎片。该序列无关的IDP功能可以反映其分子屏蔽效果。该研究检测了IDPS在淀粉样蛋白β肽（Aβ（1-42））模型系统中对原纤维形成的抑制活性。五种人类基因组衍生的IDP（尺寸范围20至44个氨基酸）显示出浓度依赖性抑制淀粉样蛋白的形成（IC50范围为60和130Ωμm，对20？μmaβ（1-42））。 IC50值比聚乙二醇和葡聚糖的两个数量级低，用作中性亲水性聚合物对照。核磁共振15≤N-标记的Aβ（1-42）揭示了Aβ（1-42）和IDP之间的相关分子相互作用。通过添加外淀粉样蛋白形成种子来消除抑制活性。因此，IDPS似乎仅在淀粉样核核阶段起作用，但不适用于伸长率。这些结果表明IDPS（0.1Ωmm或更小）具有防止易感分子的聚集的分子屏蔽效果。

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