Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions.
Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions.
复制标题
与不同纤维颤动条件相关的 β2-微球蛋白构象中间体的表征。
DOI：
--
复制
发表时间：
2011
影响因子：
2.3
通讯作者：
R. Grandori
中科院分区：
文献类型：
--
作者：
C. Santambrogio;S. Ricagno;F. Sobott;M. Colombo;M. Bolognesi;R. Grandori
β2-微球蛋白(β2M)是I类主要组织相容性复合体的轻链，也是透析相关性淀粉样变性的致病因子，其原因是其作为淀粉样物质积聚在骨骼关节中。本研究描述了β2M在两种不同的体外淀粉样蛋白形成条件下的构象特征：在20%2，2，2-三氟乙醇(TFE)存在下的中性pH和在不存在TFE时的酸性pH。电喷雾电离-质谱法(ESI-MS)分析物种分布，结合离子迁移率-质谱仪(IM-MS)、荧光和圆二色谱(CD)获得的信息。结果表明，在这两种情况下，β2m占据了完全不同的构象系综群，但两个系综群中都有一小部分群处于部分折叠状态。尽管致密性相似，但这两种部分折叠形式显示出不同的构象：在pH为7.4，20%TFe时，物种以螺旋二级结构为主，而低pH形式主要是无规卷曲。随着温度的升高，TFE中间体失去螺旋结构，变得更类似于低pH中间体。不同构象系综的存在可能解释了β2m在本文分析的两种纤颤条件下表现出的不同聚集倾向。
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.
影响因子：
7.5
作者：
Wearsch PA;Cresswell P
通讯作者：
Cresswell P
影响因子：
2.9
作者：
Eakin, CM;Knight, JD;Miranker, AD
通讯作者：
Miranker, AD
影响因子：
5.6
作者：
SAPER, MA;BJORKMAN, PJ;WILEY, DC
通讯作者：
WILEY, DC