Eukaryotic double-ring chaperonin TRiC is an ATP-dependent protein-folding machine. Most of its substrates are known to form large ordered structures from multiple polypeptide chains. Since these structures are similar to fibrillar and oligomeric forms of amyloidogenic proteins, we hypothesized that TRiC may play a role in the development of neurodegenerative diseases of amyloid nature including prion diseases. Enzyme-linked immunosorbent assay showed that monomeric, oligomeric and fibrillar forms of prion protein (PrP) bind strongly to chaperonin TRiC, whereas glycation reduces the prion protein affinity for chaperonin. Nevertheless, dynamic light scattering, electron microscopy and thioflavin T fluorescence confirmed that all studied forms of PrP undergo an amyloid transformation after interaction with chaperonin, but different forms of prion protein are capable of having different effects on the functional state of TRiC. For example, prion protein monomers completely block its ability to reactivate the chaperonin's natural substrate - sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS). At the same time, PrP oligomers and fibrils only partially prevent the reactivation of GAPDS upon the action of TRiC. The monomeric forms of prion protein glycated by methylglyoxal do not inhibit, but only slow down the chaperone-dependent reactivation of GAPDS. Thus, the interaction of amyloidogenic proteins with chaperonins could cause cell malfunction.

中文翻译：

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伴侣蛋白TRiC被天然和糖基化的ion病毒蛋白封闭。

真核双环伴侣蛋白TRiC是ATP依赖的蛋白质折叠机器。已知其大多数底物由多个多肽链形成大的有序结构。由于这些结构与淀粉样蛋白原蛋白的原纤维和寡聚形式相似，因此我们假设TRiC可能在淀粉样蛋白性神经退行性疾病（包括病毒疾病）的发展中发挥作用。酶联免疫吸附试验表明，单体，寡聚和原纤维形式的蛋白（PrP）与伴侣蛋白TRiC牢固结合，而糖基化则降低了蛋白对伴侣蛋白的亲和力。尽管如此，动态光散射，电子显微镜和硫代黄素T荧光证实，所有研究形式的PrP与伴侣蛋白相互作用后都会发生淀粉样转化，但是不同形式的of病毒蛋白对TRiC的功能状态有不同的影响。例如，病毒蛋白单体完全阻断了其重新激活伴侣蛋白天然底物-精子特异性甘油醛-3-磷酸脱氢酶（GAPDS）的能力。同时，在TRiC作用下，PrP低聚物和原纤维仅部分阻止GAPDS的重新活化。甲基乙二醛糖基化的病毒蛋白的单体形式不会抑制，而只会减慢伴侣依赖性GAPDS的活化。因此，淀粉样蛋白与伴侣蛋白的相互作用可能导致细胞功能异常。s的天然底物-精子特异的3-磷酸甘油醛脱氢酶（GAPDS）。同时，在TRiC作用下，PrP低聚物和原纤维仅部分阻止GAPDS的重新活化。甲基乙二醛糖基化的病毒蛋白的单体形式不会抑制，而只会减慢伴侣依赖性GAPDS的活化。因此，淀粉样蛋白与伴侣蛋白的相互作用可能导致细胞功能异常。s的天然底物-精子特异的3-磷酸甘油醛脱氢酶（GAPDS）。同时，在TRiC作用下，PrP低聚物和原纤维仅部分阻止GAPDS的重新活化。甲基乙二醛糖基化的病毒蛋白的单体形式不会抑制，而只会减慢伴侣依赖性GAPDS的活化。因此，淀粉样蛋白与伴侣蛋白的相互作用可能导致细胞功能异常。