Do Charge State Signatures Guarantee Protein Conformations?
Do Charge State Signatures Guarantee Protein Conformations?
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DOI：
10.1007/s13361-012-0393-z
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发表时间：
2012-07-01
影响因子：
3.2
通讯作者：
Robinson, Carol V.
中科院分区：
文献类型：
--
作者：
Hall, Zoe;Robinson, Carol V.
蛋白质在气相中在多大程度上保持其凝聚相结构是一个激烈争论的问题。与此密切相关的是观察到的电荷状态反映蛋白质构象的程度。来自电子俘获解离、氢/氢交换、离子迁移率和分子动力学的证据清楚地表明，折叠程度与电荷状态之间往往有很强的相关性，最低电荷状态观察到最紧密的构象。在这篇文章中，我们讨论了最近围绕电荷态和折叠之间的关系的争论，也集中在溶液中电荷的操纵及其对构象的影响。用来改变电荷状态的“增压”试剂可以促进电喷雾液滴的展开。然而，对于几个蛋白质复合体，增压似乎不会扰乱结构，因为没有检测到展开。因此，较高的电荷状态并不一定意味着展开。虽然电荷操纵对构象的影响仍然存在争议，但有强有力的证据表明，蛋白质的折叠、致密状态可以在气相中存活，至少在毫秒级的时间尺度上。然而，在这些紧凑状态下，侧链填料和二级结构元素的确切性质仍然难以捉摸，并促使进一步研究。
The extent to which proteins in the gas phase retain their condensed-phase structure is a hotly debated issue. Closely related to this is the degree to which the observed charge state reflects protein conformation. Evidence from electron capture dissociation, hydrogen/deuterium exchange, ion mobility, and molecular dynamics shows clearly that there is often a strong correlation between the degree of folding and charge state, with the most compact conformations observed for the lowest charge states. In this article, we address recent controversies surrounding the relationship between charge states and folding, focussing also on the manipulation of charge in solution and its effect on conformation. 'Supercharging' reagents that have been used to effect change in charge state can promote unfolding in the electrospray droplet. However for several protein complexes, supercharging does not appear to perturb the structure in that unfolding is not detected. Consequently, a higher charge state does not necessarily imply unfolding. Whilst the effect of charge manipulation on conformation remains controversial, there is strong evidence that a folded, compact state of a protein can survive in the gas phase, at least on a millisecond timescale. The exact nature of the side-chain packing and secondary structural elements in these compact states, however, remains elusive and prompts further research.