Bow-tie motifs enable protein multifunctionality by connecting cellular processes in the interactome

Cell type-specific protein interactomes are promising resources for the understanding of cell functionality and genetic perturbations in cellular states. However, while many low- and top-level aspects of interactome topology have been mapped, we still lack an understanding of the topological motifs at the intermediate level, where connectivity between cellular processes takes place. We combine conventional dendritic cell lineage 1 (cDC1)-specific expression data with a high-quality protein interactome, subsequently creating an information-rich cDC1-specifc interactome matrix that displays topological information on an unprecedented 36.7 million protein pairs at once. By dissecting the interactome-matrix, we reveal that the bow-tie motif is a major connector of cellular processes and an extremely widespread topology in the protein interactome. In aggregation, the bow-tie motifs form a scaffold within the interactome that hierarchically link cellular processes together. We further demonstrate that the bow-tie motif9s design can enable protein multifunction. Our generic approach allows a topological characterization and visualization of any large network, facilitating a more effective usage of community-produced interaction data, and is applicable to any cell type9s interactome.