Biology subjects

Monsellier, E.

Publications and source records attributed to Monsellier, E..

5 recordsLinked to original sources

bioRxiv2026

A quantitative interactome map reveals affinity tailored hijacking of human cellular functions by resident and pathogenic bacteria

Bacteria employ molecular mimicry to hijack host cellular functions for their own benefit. Despite the wealth of data mapping human-bacteria interactions, a comprehensive view of how these networks are fine-tuned remains elusive. In particular, there have been no large-scale screenings measuring human-bacterial protein-protein binding affinities to explore their role in functional and pathological outcomes. Here, we report the largest quantitative interactome to date between the family of human PDZ domains and C-terminal PDZ-binding motifs (PBMs) in effectors from pathogenic and resident gut bacteria. We show that bacteria tailor effector sequences to bind PDZ domains with similar or higher binding affinities than human PBMs to hijack their associated cellular functions. For a subset of the dataset, we validate PDZ-PBM interactions with the corresponding full-length proteins and show that for pathogenic E. coli effector NleA, its C-terminal PBM is necessary for interactions with proteins involved in intracellular transport and membrane organization, probably impacting the host glycocalyx to favor infection. Finally, we show that motifs overlapping with effector PBMs target interaction modules other than PDZ domains, adding an additional layer of complexity to the host-microbe molecular dialogue.

systems biology↗

bioRxiv2026

Interdependent androgen and glucocorticoid receptor signalling shapes prostate epithelial homeostasis

Androgen signalling is essential for prostate secretory functions and epithelial cell maintenance, yet how this signal is translated into a transcriptional output remains poorly understood. Androgens functions are primarily mediated by the androgen receptor (AR), which binds hormone response elements similar to those of other steroid receptors, including the glucocorticoid receptor (GR). Here we show that AR and GR are co-expressed in the prostate epithelium, and co-located within nuclear foci. Moreover, GR promotes the formation and dynamics of AR nuclear condensates, and heterodimerizes with AR in a ligand-binding domain-dependent manner. In addition, subtle variations within the hormone response element sequence direct the co-recruitment of AR and GR into activator or repressor complexes to activate or repress gene expression. Finally, prostate-specific deletion of GR in mice disrupts AR nuclear distribution, impairs AR-dependent gene networks involved in epithelial maintenance, and promotes the expression of genes involved in metabolism and cell cycle, resulting in altered tissue homeostasis. Thus, these findings identify GR as an integral component of the AR transcriptional machinery in epithelial cells of the healthy prostate, and reveal how shared cis-regulatory elements are interpreted to generate distinct transcriptional outcomes.

cell biology↗

bioRxiv2022

The Holdup Multiplex, an assay for high-throughput measurement of protein-ligand affinity constants using a mass-spectrometry readout

The accurate description and subsequent modeling of protein interactomes requires quantification of their affinities at proteome-wide scale. Here we develop and validate the Holdup Multiplex, a versatile assay for high-throughput measurement of protein-ligand affinity constants that uses mass-spectrometry as readout. The method can quantify thousands of affinities in one single run, with high precision and over several orders of magnitude. We applied this strategy to the seven human 14-3-3 isoforms, quantifying in a few sample-runs their interaction with 1,000 different phosphopeptides. We were able to identify hundreds of new 14-3-3 binding sites. We showed that the seven human 14-3-3 display similar specificities but staggered affinities, 14-3-3g being always the best binder and 14-3-3{varepsilon} and {sigma}, the weakest. Finally, we identified dozens of 14-3-3 bindings sites, some intervening in key signaling pathways, that were either stabilized or destabilized by the phytotoxin Fusicoccin-A. Our approach, which throughput can be pushed up to the sensitivity limit of the mass-spectrometry setup, is applicable to any category of protein-ligand interactions and thus bears a wide potential both for high-throughput interactomics and chemoproteomics.

systems biology↗

bioRxiv2022

ProFeatMap: a customizable tool for 2D feature representation of protein sets

SummaryHere, we present ProFeatMap, an intuitive Python-based website allowing to quickly display protein features such as domains, repeats, post-translational modifications location and so forth, into a highly customizable graphical 2D map. Starting from a user-defined protein list, ProFeatMap automatically extracts the main protein features from the Uniprot database. The resulting high-quality maps can help to gain insights, e.g. feature redundancy, that were previously overlooked but which may be useful for the research project. ProFeatMap is freely accessible on the web at: https://profeatmap.pythonanywhere.com/ AvailabilitySource code is freely accessible at https://github.com/profeatmap/ProFeatMap under the GPL license. Contactbichg@igbmc.fr, yves.nomine@igbmc.fr Supplementary informationdetailed user guide of ProFeatMap

bioinformatics↗

bioRxiv2021

Quantitative fragmentomics allow affinity mapping of interactomes

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 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.

systems biology↗