关键词: affinity purification interactome interologs modifiers notch pathway protein interaction proteome

来  源:   DOI:10.1016/j.devcel.2024.06.002

Abstract:
We describe a next-generation Drosophila protein interaction map-\"DPIM2\"-established from affinity purification-mass spectrometry of 5,805 baits, covering the largest fraction of the Drosophila proteome. The network contains 32,668 interactions among 3,644 proteins, organized into 632 clusters representing putative functional modules. Our analysis expands the pool of known protein interactions in Drosophila, provides annotation for poorly studied genes, and postulates previously undescribed protein interaction relationships. The predictive power and functional relevance of this network are probed through the lens of the Notch signaling pathway, and we find that newly identified members of complexes that include known Notch modifiers can also modulate Notch signaling. DPIM2 allows direct comparisons with a recently published human protein interaction network, defining the existence of functional interactions conserved across species. Thus, DPIM2 defines a valuable resource for predicting protein co-complex memberships and functional associations as well as generates functional hypotheses regarding specific protein interactions.
摘要:
我们描述了下一代果蝇蛋白相互作用图-“DPIM2”-从5,805个诱饵的亲和纯化-质谱建立,覆盖果蝇蛋白质组的最大部分。该网络包含3,644种蛋白质之间的32,668种相互作用,组织成632个集群,代表假定的功能模块。我们的分析扩展了果蝇中已知蛋白质相互作用的库,为研究不足的基因提供注释,并假设以前未描述的蛋白质相互作用关系。该网络的预测能力和功能相关性通过Notch信号通路的透镜来探测,我们发现新鉴定的包括已知Notch修饰剂的复合物成员也可以调节Notch信号传导。DPIM2允许与最近发表的人类蛋白质相互作用网络进行直接比较,定义跨物种保守的功能相互作用的存在。因此,DPIM2定义了预测蛋白质共复合物成员和功能关联的有价值的资源,并生成了关于特定蛋白质相互作用的功能假设。
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