心脏组织中蛋白质构象和超复合物的化学交联质谱分析。
Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue.
机构信息
Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
Department of Bioengineering, University of Washington, Seattle, WA 98105, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98105, USA; Mitochondria and Metabolism Center, University of Washington, Seattle, WA 98105, USA.
出版信息
Cell Syst. 2018 Jan 24;6(1):136-141.e5. doi: 10.1016/j.cels.2017.10.017. Epub 2017 Nov 29.
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 nonexistent. Here, we demonstrate the application of crosslinking mass spectrometry to identify protein structural features and interactions in tissue samples, providing systems structural biology insight into protein complexes as they exist in the mouse heart. This includes insights into multiple conformational states of sarcomere proteins, as well as interactions among OXPHOS complexes indicative of supercomplex assembly. The extension of crosslinking mass spectrometry analysis into the realm of tissues opens the door to increasing our understanding of protein structures and interactions within the context of the greater biological system.
虽然现代结构生物学技术极大地扩展了可研究的蛋白质复合物的大小和类型，但实际上，我们还无法从组织中获取关于蛋白质和复合物的大规模结构信息。在这里，我们展示了交联质谱在鉴定组织样品中蛋白质结构特征和相互作用方面的应用，为我们提供了关于蛋白质复合物在小鼠心脏中存在状态的系统结构生物学见解。这包括肌节蛋白的多种构象状态的见解，以及表明 OXPHOS 复合物组装的超复合物相互作用。交联质谱分析扩展到组织领域，为我们增加对蛋白质结构和相互作用在更大生物系统中的理解打开了大门。
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