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首页> 外文期刊>Journal of mass spectrometry: JMS >Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions
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Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions

机译：与不同原纤化条件相关的β2-微球蛋白构象中间体的表征

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摘要

β2-Microglobulin (β2m) is the light chain of the class-I major histocompatibility complex, being also the causing agent of dialysis-related amyloidosis, which results from its accumulation as amyloid material in the skeletal joints. This study describes conformational properties of β2m under two distinct, in vitro amyloidogenic conditions: neutral pH in the presence of 20% 2,2,2-trifluoroethanol (TFE) and acidic pH in the absence of TFE. Species distribution analysis by electrospray ionization-mass spectrometry (ESI-MS) is combined with information obtained by ion mobility-mass spectrometry (IM-MS), fluorescence and circular dichroism (CD) spectroscopy. It is shown that β2m populates quite different conformational ensembles under the two conditions, but both ensembles display a minor fraction of the population in a partially folded state. In spite of similar compactness, these two partially folded forms display different conformations: helical secondary structure is predominant in the species at pH 7.4, 20% TFE, while the low-pH form is mainly random coil. As temperature is increased, the TFE intermediate looses helical structure becoming more similar to the low-pH intermediate. The existence of different conformational ensembles may rationalize the different aggregation propensity displayed by β2m under the two fibrillation conditions analyzed here.
机译：β2-微球蛋白（β2m）是I类主要组织相容性复合体的轻链，也是透析相关淀粉样变性病的病原体，这是由于其作为淀粉样物质在骨骼关节中的积累而产生的。这项研究描述了在两种不同的体外淀粉样蛋白生成条件下β2m的构象性质：存在20％2,2,2-三氟乙醇（TFE）的中性pH和没有TFE的酸性pH。通过电喷雾电离质谱（ESI-MS）进行物种分布分析，并结合通过离子迁移质谱（IM-MS），荧光和圆二色性（CD）光谱获得的信息。结果表明，在这两种条件下，β2m组成的构象团完全不同，但两个团簇都以部分折叠状态显示少数群体。尽管具有相似的紧密度，但这两种部分折叠的形式仍显示出不同的构象：在pH 7.4、20％TFE的物种中，螺旋二级结构占主导地位，而低pH形式则主要是无规卷曲。随着温度升高，TFE中间体失去螺旋结构，变得与低pH中间体更相似。在本文分析的两种原纤化条件下，不同构象合体的存在可能使β2m表现出的不同聚集倾向合理化。

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