Complete Topological Mapping of a Cellular Protein Interactome Reveals Bow-Tie Motifs as Ubiquitous Connectors of Protein Complexes

Cell Rep. 2020 Jun 16;31(11):107763. doi: 10.1016/j.celrep.2020.107763.


The network topology of a protein interactome is shaped by the function of each protein, making it a resource of functional knowledge in tissues and in single cells. Today, this resource is underused, as complete network topology characterization has proved difficult for large protein interactomes. We apply a matrix visualization and decoding approach to a physical protein interactome of a dendritic cell, thereby characterizing its topology with no prior assumptions of structure. We discover 294 proteins, each forming topological motifs called "bow-ties" that tie together the majority of observed protein complexes. The central proteins of these bow-ties have unique network properties, display multifunctional capabilities, are enriched for essential proteins, and are widely expressed in other cells and tissues. Collectively, the bow-tie motifs are a pervasive and previously unnoted topological trend in cellular interactomes. As such, these results provide fundamental knowledge on how intracellular protein connectivity is organized and operates.

Keywords: biological networks; bow-tie; essential; functional organization; knot protein; multifunctional; network motifs; network topology; protein complex; topological overlap.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Computational Biology / methods
  • Humans
  • Mice
  • Models, Biological*
  • Protein Interaction Mapping* / methods
  • Proteins / metabolism*
  • Signal Transduction / physiology*


  • Proteins