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Journal Articles Nature Communications Year : 2022

Quantitative fragmentomics allow affinity mapping of interactomes

Gergo Gogl
Boglarka Zambo
Camille Kostmann
  • Function : Author
Alexandra Cousido-Siah
  • Function : Author
Bastien Morlet
Fabien Durbesson
  • Function : Author
Luc Negroni
Pascal Eberling
  • Function : Author
Pau Jané
  • Function : Author
Yves Nominé
Andras Zeke
Søren Østergaard
Élodie Monsellier
  • Function : Author
Renaud Vincentelli
  • Function : Author

Abstract

Abstract Human protein networks have been widely explored but most binding affinities remain unknown, hindering quantitative interactome-function studies. Yet interactomes rely on minimal interacting fragments displaying quantifiable affinities. Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. We calculate interactomic distances, identify hot spots for viral interference, generate binding profiles and specificity logos, and explain selected cases by crystallographic studies. Mass spectrometry experiments on cell extracts and literature surveys show that quantitative fragmentomics effectively complements protein interactomics by providing affinities and completeness of coverage, putting a full human interactome affinity survey within reach. Finally, we show that interactome hijacking by the viral PBM of human papillomavirus E6 oncoprotein substantially impacts the host cell proteome beyond immediate E6 binders, illustrating the complex system-wide relationship between interactome and function.

Dates and versions

hal-04304685 , version 1 (24-11-2023)

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Gergo Gogl, Boglarka Zambo, Camille Kostmann, Alexandra Cousido-Siah, Bastien Morlet, et al.. Quantitative fragmentomics allow affinity mapping of interactomes. Nature Communications, 2022, 13 (1), pp.5472. ⟨10.1038/s41467-022-33018-0⟩. ⟨hal-04304685⟩
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