Quantitative Evaluation of Native Protein Folds and Assemblies by Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS).
Quantitative Evaluation of Native Protein Folds and Assemblies by Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS).
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DOI：
10.1007/s13361-018-2070-3
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发表时间：
2019-01
影响因子：
3.2
通讯作者：
Borysik AJ
中科院分区：
文献类型：
--
作者：
Harris MJ;Raghavan D;Borysik AJ
氢-氘交换质谱法（HDX-MS）对蛋白质结构主动性具有重要的潜力，但其与蛋白质构象的关系尚不清楚。我们报告了HDX- ms区分天然和非天然蛋白质的功效，使用了一种流行的方法来计算蛋白质结构中的HDX保护因子（PFs）。HDX-MS识别天然蛋白质构象的能力通过二元结构分类进行量化，从而可以量化和更好地理解蛋白质建模方法的优点。我们表明，高度精确的PF计算并不是能够有效区分天然和非天然蛋白质折叠的HDX-MS模拟的先决条件。模拟也可以直接在独特的结构上进行，便于对许多替代构象进行高通量评估。HDX-MS对同源蛋白组装的构象进行分类的能力也进行了研究。与蛋白质单体相反，我们发现这些系统的模拟和实验HDX-MS数据之间明显缺乏对应关系，从而导致HDX-MS识别天然状态的能力下降。然而，我们展示了令人惊讶的高诊断能力的模拟数据的组装，其中很大比例的单个链占据蛋白质-蛋白质界面。我们将此与可以采样替代亚基取向的肽的数量联系起来，并在应用HDX-MS评估蛋白质结构的更大背景下讨论这些观察结果。本文的在线版本（10.1007/s13361-018-2070-3）包含补充资料，授权用户可使用。
Hydrogen deuterium exchange mass spectrometry (HDX-MS) has significant potential for protein structure initiatives but its relationship with protein conformations is unclear. We report on the efficacy of HDX-MS to distinguish between native and non-native proteins using a popular approach to calculate HDX protection factors (PFs) from protein structures. The ability of HDX-MS to identify native protein conformations is quantified by binary structural classification such that merits of the approach for protein modelling can be quantified and better understood. We show that highly accurate PF calculations are not a prerequisite for HDX-MS simulations that are capable of effectively discriminating between native and non-native protein folds. The simulations can also be performed directly on unique structures facilitating high-throughput evaluation of many alternate conformations. The ability of HDX-MS to classify the conformations of homo-protein assemblies is also investigated. In contrast to protein monomers, we show a significant lack of correspondence between the simulated and experimental HDX-MS data for these systems with a subsequent decrease in the ability of HDX-MS to identify native states. However, we demonstrate surprisingly high diagnostic ability of the simulated data for assemblies in which a significant proportion of the individual chains occupy protein-protein interfaces. We relate this to the number of peptides that can sample alternate subunit orientations and discuss these observations within the larger context of applying HDX-MS to evaluate protein structures. Graphical Abstract The online version of this article (10.1007/s13361-018-2070-3) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
Schneidman-Duhovny D;Inbar Y;Nussinov R;Wolfson HJ
通讯作者：
Wolfson HJ
影响因子：
6.8
作者：
Marciano, David P.;Dharmarajan, Venkatasubramanian;Griffin, Patrick R.
通讯作者：
Griffin, Patrick R.
影响因子：
8
作者：
Urakubo, Yoshiaki;Ikura, Teikichi;Ito, Nobutoshi
通讯作者：
Ito, Nobutoshi
DOI：
10.1107/s0907444998010865
发表时间：
1999-02-01
影响因子：
2.2
作者：
Martin, C;Richard, V;Mauguen, Y
通讯作者：
Mauguen, Y
影响因子：
2.9
作者：
Mashiach-Farkash, Efrat;Nussinov, Ruth;Wolfson, Haim J.
通讯作者：
Wolfson, Haim J.