Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.
Cell Syst. 2017 May 24;4(5):483-494. doi: 10.1016/j.cels.2017.04.006.
Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors. Commander is critical for vertebrate embryogenesis, and defects in the complex and its interaction partners disrupt craniofacial, brain, and heart development. Here, we review the synergy between large-scale proteomic efforts and focused studies in the discovery of Commander, describe its composition, structure, and function, and discuss how it illustrates the power of systems biology. Based on 3D modeling and biochemical data, we draw strong parallels between Commander and the retromer cargo-recognition complex, laying a foundation for future research into Commander's role in human developmental disorders.
近期的人类相互作用组质谱图谱独立证实了一个大型多蛋白复合物的存在，该复合物被称为“指挥官”。该复合物在动物中广泛保守，迄今为止在几乎所有检查过的人类细胞类型中都普遍表达，因此它可能发挥着基本的细胞功能，类似于其他参与表达、蛋白质稳态和运输的普遍存在的机器。对个别亚基的实验支持其在核内体蛋白分拣中的作用，包括 Notch 蛋白、铜转运蛋白和脂蛋白受体的运输。指挥官对于脊椎动物胚胎发生至关重要，复合物及其相互作用伙伴的缺陷会破坏颅面、大脑和心脏的发育。在这里，我们综述了大规模蛋白质组学研究与集中研究在发现指挥官方面的协同作用，描述了它的组成、结构和功能，并讨论了它如何说明了系统生物学的力量。基于 3D 建模和生化数据，我们在指挥官和逆行运输货物识别复合物之间建立了很强的相似性，为未来研究指挥官在人类发育障碍中的作用奠定了基础。
