The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes.
The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes.
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DOI：
10.1016/j.str.2013.06.004
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发表时间：
2013-08-06
期刊：
影响因子：
5.7
通讯作者：
Robinson, Carol V.
中科院分区：
文献类型：
--
作者：
Hall, Zoe;Hernandez, Helena;Marsh, Joseph A.;Teichmann, Sarah A.;Robinson, Carol V.
质谱法可用于表征多蛋白复合物，定义其亚基化学计量学和溶液破裂和碰撞诱导解离（CID）后的组成。虽然蛋白质复合物在气相中的CID通常会导致未折叠亚基的解离，但第二种非典型途径是可能的，其中紧凑的亚基或亚复合物被弹出而不展开。因为三级结构和亚基的相互作用可以保留，这是结构研究的首选途径。我们如何影响采用哪条途径？通过研究一系列同质和异质蛋白质复合物的性质及其在溶液中总电荷的变化，我们发现低亚基柔韧性、较高的电荷密度、较少的盐桥和较小的界面可能参与促进解离途径而不展开。因此，操纵蛋白质复合物上的电荷使我们能够通过模拟溶液中所遵循的结构信息途径来指导解离。离子迁移-质谱法用于探测解离产物的结构高电荷态喷射致密单体和二聚体盐桥和电荷密度是决定解离途径的重要因素，为蛋白质复合物提供具有结构信息的气相解离途径是结构质谱法的主要目标。Hall等人建立了蛋白质结构和解离途径之间的相关性，可用于预测和控制对气相活化的反应。
Mass spectrometry can be used to characterize multiprotein complexes, defining their subunit stoichiometry and composition following solution disruption and collision-induced dissociation (CID). While CID of protein complexes in the gas phase typically results in the dissociation of unfolded subunits, a second atypical route is possible wherein compact subunits or subcomplexes are ejected without unfolding. Because tertiary structure and subunit interactions may be retained, this is the preferred route for structural investigations. How can we influence which pathway is adopted? By studying properties of a series of homomeric and heteromeric protein complexes and varying their overall charge in solution, we found that low subunit flexibility, higher charge densities, fewer salt bridges, and smaller interfaces are likely to be involved in promoting dissociation routes without unfolding. Manipulating the charge on a protein complex therefore enables us to direct dissociation through structurally informative pathways that mimic those followed in solution. Comparison of gas and solution disassembly routes of multiprotein complexes Ion mobility-mass spectrometry used to probe structures of dissociation products High charge states eject compact monomers and dimers Salt bridges and charge density are important for dictating dissociation pathway Producing structurally informative gas-phase dissociation pathways for protein complexes is a major goal of structural mass spectrometry. Hall et al. establish correlations between protein structure and dissociation pathways that can be used to predict and control the response to activation in the gas phase.
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影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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