Quantitative fragmentomics allow affinity mapping of interactomes
2022
Gogl, Gergo | Zambo, Boglarka | Kostmann, Camille | Cousido-Siah, Alexandra | Morlet, Bastien | Durbesson, Fabien | Negroni, Luc | Eberling, Pascal | Jané, Pau | Nominé, Yves | Zeke, Andras | Østergaard, Søren | Monsellier, Élodie | Vincentelli, Renaud | Travé, Gilles | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Architecture et fonction des macromolécules biologiques (AFMB) ; Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Research Centre for Natural Sciences ; Hungarian Academy of Sciences (MTA) | Novo Nordisk Inc ; NOVO NORDISK PARK | ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010) | ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017) | ANR-18-CE92-0017,UBE3A,Ubiquitine-ligase E6AP: Analyse structurale et modulation par de petites molécules.(2018) | ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010) | ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020)
International audience
Показать больше [+] Меньше [-]Английский. 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.
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Эту запись предоставил Institut national de la recherche agronomique
