Chapron Yves, Charlet Laurent, Sahai Nita
a AIED, Research , 108 rue du puy, La Terrasse , 38660 , France .
J Biomol Struct Dyn. 2014;32(11):1802-16. doi: 10.1080/07391102.2013.836461. Epub 2013 Oct 23.
Pathogenic prion protein scrapie (PrP(sc)) may contaminate soils for decades and remain in water in colloidal suspension, providing infection pathways for animals through the inhalation of ingested dust and soil particles, and drinking water. We used molecular dynamics simulations to understand the strong binding mechanism of this pathogenic peptide with clay mineral surfaces and compared our results to experimental works. We restricted our model to the moiety PrP(92-138), which is a portion of the whole PrP(sc) molecule responsible for infectivity and modeled it using explicit solvating water molecules in contact with a pyrophyllite cleavage plane. Pyrophyllite is taken as a model for common soil clay, but it has no permanent structural charge. However, partial residual negative charges occur on the cleavage plane slab surface due to a slab charge unbalance. The charge is isotropic in 2D and it was balanced with K(+) ions. After partially removing potassium ions, the peptide anchors to the clay surface via up to 10 hydrogen bonds, between protonated lysine or histidine residues and the oxygen atoms of the siloxane cavities. Our results provide insight to the mechanism responsible for the strong association between the PrP(sc) peptide and clay nanoparticles and the associations present in contaminated soil and water which may lead to the infection of animals.
致病性朊病毒蛋白瘙痒病（PrP(sc)）可能会在土壤中污染数十年，并以胶体悬浮液的形式存在于水中，通过吸入摄入的灰尘和土壤颗粒以及饮用水为动物提供感染途径。我们使用分子动力学模拟来了解这种致病肽与粘土矿物表面的强结合机制，并将我们的结果与实验工作进行比较。我们将模型限制在PrP(92 - 138)部分，这是整个PrP(sc)分子中负责感染性的一部分，并使用与叶蜡石解理面接触的显式溶剂化水分子对其进行建模。叶蜡石被用作常见土壤粘土的模型，但它没有永久的结构电荷。然而，由于板电荷不平衡，在解理面板表面会出现部分残余负电荷。电荷在二维中是各向同性的，并用K(+)离子进行平衡。在部分去除钾离子后，该肽通过质子化的赖氨酸或组氨酸残基与硅氧烷腔的氧原子之间多达10个氢键锚定在粘土表面。我们的结果为PrP(sc)肽与粘土纳米颗粒之间的强关联机制以及受污染土壤和水中存在的可能导致动物感染的关联提供了见解。
