Chemical cross-linking mass spectrometry for systems structural biology in mouse heart tissue.

While modern structural biology technologies have greatly expanded the size and type of protein complexes that can now be studied, the ability to derive large-scale structural information on proteins and complexes as they exist within tissues is practically non-existent. Many protein properties and their involvement in disease pathways are not replicated in cell culture and some complexes are not amenable to purification. Thus, the lack of tissue-level structural information limits molecular-level insight on diseases such as heart failure. Here we demonstrate the application of XL-MS to identify protein structural features and interactions in tissue samples, providing the first systems structural biology insight on protein complexes as they exist in the mouse heart.

尽管现代结构生物学技术极大拓展了当前可研究的蛋白质复合物的规模与类型，但获取蛋白质及其复合物在天然组织环境中的大规模结构信息的能力，实则几乎为零。诸多蛋白质特性及其在疾病通路中的参与过程无法在细胞培养体系中重现，且部分复合物难以实现纯化。因此，组织层面结构信息的缺失，限制了我们对心力衰竭等疾病的分子层面认知。本研究展示了交联质谱（Cross-Linking Mass Spectrometry，XL-MS）在组织样本中鉴定蛋白质结构特征与相互作用的应用，首次从系统结构生物学视角解析了小鼠心脏中原生状态的蛋白质复合物。