A Mass-Spectrometry-Based Modelling Workflow for Accurate Prediction of IgG Antibody Conformations in the Gas Phase.
A Mass-Spectrometry-Based Modelling Workflow for Accurate Prediction of IgG Antibody Conformations in the Gas Phase.
复制标题
基于质谱的建模工作流程，用于准确预测气相中IgG抗体构象。
DOI：
10.1002/anie.201812018
复制
发表时间：
2018-12-21
期刊：
影响因子：
--
通讯作者：
Politis A
中科院分区：
文献类型：
--
作者：
Hansen K;Lau AM;Giles K;McDonnell JM;Struwe WB;Sutton BJ;Politis A
免疫球蛋白是参与防御外来物质的生物分子。柔性是其与抗原结合和受体相互作用相关的功能特性的关键。我们开发了一种结合离子迁移质谱（IM-MS）和分子建模的综合策略，以研究人IgG抗体的构象动力学。组装了所有四种人IgG亚类的预测模型，并在IM-MS期间从扩展状态过渡到塌陷状态时对其动力学进行了采样。我们的数据暗示IgG抗体的这种塌陷与其内在结构特征有关，包括Fab臂柔性、向Fc区塌陷以及其铰链区的长度。这里提出的工作流程提供了与这些柔性IgG分子的观察到的碰撞横截面良好一致的准确结构表示。这些结果对研究其他非小叶柔性蛋白具有启示意义。
Immunoglobulins are biomolecules involved in defence against foreign substances. Flexibility is key to their functional properties in relation to antigen binding and receptor interactions. We have developed an integrative strategy combining ion mobility mass spectrometry (IM‐MS) with molecular modelling to study the conformational dynamics of human IgG antibodies. Predictive models of all four human IgG subclasses were assembled and their dynamics sampled in the transition from extended to collapsed state during IM‐MS. Our data imply that this collapse of IgG antibodies is related to their intrinsic structural features, including Fab arm flexibility, collapse towards the Fc region, and the length of their hinge regions. The workflow presented here provides an accurate structural representation in good agreement with the observed collision cross section for these flexible IgG molecules. These results have implications for studying other nonglobular flexible proteins.
登录
查看更多内容
影响因子：
5.6
作者：
Harris, LJ;Skaletsky, E;McPherson, A
通讯作者：
McPherson, A
影响因子：
14.8
作者：
Hernandez, Helena;Robinson, Carol V.
通讯作者：
Robinson, Carol V.
影响因子：
5.7
作者：
Eschweiler, Joseph D.;Farrugia, Mark. A.;Ruotolo, Brandon T.
通讯作者：
Ruotolo, Brandon T.
影响因子：
4.3
作者：
Goeth, Melanie;Pagel, Kevin
通讯作者：
Pagel, Kevin
影响因子：
46.9
作者：
Jakobovits, Aya;Amad, Rafael G.;Schwab, Gisela
通讯作者：
Schwab, Gisela