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首页> 外文期刊>Electrophoresis: The Official Journal of the International Electrophoresis Society >The influence of Cu(2+) on the unfolding and refolding of intact and proteolytically processed beta(2)-microglobulin.
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The influence of Cu(2+) on the unfolding and refolding of intact and proteolytically processed beta(2)-microglobulin.

机译：Cu（2+）对完整和蛋白水解处理的β（2）-微球蛋白的展开和重新折叠的影响。

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摘要

Human beta(2)-microglobulin (beta(2)m) is an amyloidogenic protein in patients suffering from chronic kidney disease and especially in those patients that need intermittent hemodialysis for longer periods, e.g., when awaiting transplantation. While many in vitro conditions induce beta(2)m-amyloid formation from wild-type (wt) beta(2)m and while a number of structurally altered beta(2)m molecules are known to be conformationally unstable and amyloidogenic on their own, it is not known why beta(2)m-amyloid is generated in some dialysis patients. For many amyloid proteins it is known that divalent metal ions, especially Cu(2+), display strong binding and distinct destabilizing effects on protein conformation. The present study uses CE to assess conformational states of wt and cleaved beta(2)m (dK58-beta(2)m, beta(2)m cleaved at lysine-58, a modification found in the circulation of hemodialysis patients) in the presence of divalent metal ions. The experiments provide both qualitative and quantitative data showing the specific destabilizing effects of Cu(2+)-ions on the folding of wt beta(2)m. Both refolding after acid denaturation and solution structure of beta(2)m under otherwise native conditions are severely influenced by Cu(2+). An increased unfolding, aggregation, and induction of Congo red-reactive molecular species in Cu(2+)-incubated wt-beta(2)m could be demonstrated while the refolding kinetics of dK58-beta(2)m, already slower than the wt molecule, appeared not to be further decreased by Cu(2+). Given the interest in the actions of metal ions in other types of amyloidosis, including, e.g., Alzheimer's disease and the prion encephalopathies, the use of microelectrophoretic methods to monitor unfolding and refolding of biomolecules available in scarce amounts as shown in this study is an attractive option.
机译：人β（2）-微球蛋白（β（2）m）在患有慢性肾脏疾病的患者中，尤其是在需要长时间进行间歇性血液透析的患者中（例如在等待移植时）是一种淀粉样蛋白。虽然许多体外条件诱导野生型（wt）beta（2）m形成beta（2）m-淀粉样蛋白，而许多结构改变的beta（2）m分子本身构象不稳定且具有淀粉样生成作用，尚不清楚为什么在某些透析患者中​​会生成β（2）m-淀粉样蛋白。对于许多淀粉样蛋白，已知二价金属离子，尤其是Cu（2+），对蛋白构象显示强结合力和独特的去稳定作用。本研究使用CE来评估wt和裂解的beta（2）m（dK58-beta（2）m，在赖氨酸58裂解的beta（2）m的构象状态），这是血液透析患者循环中发现的一种修饰）。二价金属离子的存在。实验提供定性和定量数据，显示Cu（2+）离子对wt beta（2）m折叠的特定去稳定作用。酸变性后的重新折叠和在其他天然条件下β（2）m的溶液结构都受到Cu（2+）的严重影响。可以证明在Cu（2+）孵育的wt-beta（2）m中刚果红色反应分子种类增加了展开，聚集和诱导，而dK58-beta（2）m的重折叠动力学已经比慢。 wt分子似乎并没有被Cu（2+）进一步降低。鉴于人们对金属离子在其他类型的淀粉样变性病（包括阿尔茨海默氏病和the病毒性脑病）中的作用产生了兴趣，如本研究所示，使用微电泳方法来监测稀有量的可用生物分子的展开和再折叠是有吸引力的选项。

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