Author:
Gogl Gergo,Zambo Boglarka,Kostmann Camille,Cousido-Siah Alexandra,Morlet Bastien,Durbesson Fabien,Negroni Luc,Eberling Pascal,Jane Pau,Nomine Yves,Zeke Andras,Østergaard Søren,Monsellier Elodie,Vincentelli Renaud,Trave Gilles
Abstract
AbstractHuman 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 measured 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 complement protein interactomics by providing affinities and completeness of coverage, putting a full human interactome affinity survey within realistic reach. Finally, we show that interactome hijacking by the viral PBM of human papillomavirus (HPV) E6 oncoprotein deeply impacts the host cell proteome way beyond immediate E6 binders, illustrating the complex system-wide relationship between interactome and function.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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