Relating gas phase to solution conformations: Lessons from disordered proteins.

Relating gas phase to solution conformations: Lessons from disordered proteins.
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DOI:
10.1002/pmic.201400605
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发表时间:
2015-08
期刊:
影响因子:
3.4
通讯作者:
Barran PE
Barran PE
中科院分区:
生物学3区
文献类型:
--
作者:
Beveridge R;Phillips AS;Denbigh L;Saleem HM;MacPhee CE;Barran PE

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近年来,质谱(MS)和离子迁移质谱(IM-MS)都已被开发为研究缺乏固定三级结构但可能含有瞬时形成二级结构元件的区域的蛋白质的技术,即内在无序蛋白质(IDP)。IM-MS是研究IDP的合适方法,它提供了对溶液中存在的构象的深入了解,可能使低密度结构形式的分析成为可能。在这里,我们描述了两种IDP的IM-MS数据;与帕金森病有关的α-突触核蛋白(α-Syn)和与心血管疾病有关的载脂蛋白C-II(ApoC-II)。我们报告了ApoC‐II在气相中行为方式的明显差异。虽然大多数IDP,包括α-Syn,存在于许多电荷状态和广泛的旋转平均碰撞截面(CCS)中,但ApoC-II仅存在于四种电荷状态和非常窄的CCS范围中,与溶液条件无关。在这里,我们比较了两种蛋白质的MS和IM-MS数据,并根据它们可能坚持的不同电离过程合理化了蛋白质之间的差异。
In recent years both mass spectrometry (MS) and ion mobility mass spectrometry (IM‐MS) have been developed as techniques with which to study proteins that lack a fixed tertiary structure but may contain regions that form secondary structure elements transiently, namely intrinsically disordered proteins (IDPs). IM‐MS is a suitable method for the study of IDPs which provides an insight to conformations that are present in solution, potentially enabling the analysis of lowly populated structural forms. Here, we describe the IM‐MS data of two IDPs; α‐Synuclein (α‐Syn) which is implicated in Parkinson's disease, and Apolipoprotein C‐II (ApoC‐II) which is involved in cardiovascular diseases. We report an apparent discrepancy in the way that ApoC‐II behaves in the gas phase. While most IDPs, including α‐Syn, present in many charge states and a wide range of rotationally averaged collision cross sections (CCSs), ApoC‐II presents in just four charge states and a very narrow range of CCSs, independent of solution conditions. Here, we compare MS and IM‐MS data of both proteins, and rationalise the differences between the proteins in terms of different ionisation processes which they may adhere to.