Next-generation Drosophila protein interactome map and its functional implications

Dev Cell. 2024 Sep 23;59(18):2506-2517.e6. doi: 10.1016/j.devcel.2024.06.002. Epub 2024 Jun 28.

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.

Keywords: affinity purification; interactome; interologs; modifiers; notch pathway; protein interaction; proteome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster
  • Gene Regulatory Networks
  • Humans
  • Protein Binding
  • Protein Interaction Maps*
  • Proteome / genetics
  • Proteome / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Proteome