Biology subjects

Depenveiller, C.

Publications and source records attributed to Depenveiller, C..

3 recordsLinked to original sources

bioRxiv2026

PP-MAPS: dynamic pharmacophore signatures of protein-peptide interfaces from molecular dynamics trajectories

Protein-peptide interactions underlie many cellular signaling and regulatory processes and are increasingly exploited in drug discovery. Characterizing such interfaces often requires the analysis of ensembles of conformations obtained by molecular modeling or molecular dynamics (MD) simulations, where transient contacts and alternative binding modes can be critical. Pharmacophore models provide an intuitive, transferable representation of molecular interactions. Dynophore i.e. "dynamic pharmacophore" approaches have been developed for small-molecule ligands with MD information. We present PP-MAPS (Protein-Peptide Molecular dynamics Assisted Pharmacophore Signatures), an open-source workflow that extracts and aggregates pharmacophore interactions along MD trajectories of protein-peptide complexes. PP-MAPS produces per-residue interaction frequencies and pharmacophore heatmaps that facilitate comparison of peptides, binding sites and receptor variants. PP-MAPS is implemented in Python and is available under an open-source license at https://github.com/camilledepenveiller/PP-MAPS. The workflow relies on GROMACS for trajectory processing and can use either LigandScout or the Chemical Data Processing Toolkit (CDPKit) for pharmacophore feature detection.

bioinformatics↗

bioRxiv2025

Sphingolipid-driven interleaflet coupling orchestrates Rho-GTPase recruitment to nanodomains for signal activation in plants

Biological membranes are both laterally heterogeneous and asymmetrical across leaflets, yet how this asymmetry contributes to signal transduction remains unclear. Here we show that sphingolipid-driven interleaflet coupling coordinates nanodomain organization and Rho-GTPase activation in plants. Using molecular dynamics simulations, super-resolution and single-molecule imaging, quantitative genetics, and biochemistry, we find that very long acyl chain (VLCFA)-containing sphingolipids in the outer leaflet interdigitate with phosphatidylserine (PS) in the inner leaflet, forming a vertical molecular bridge that organizes PS into nanodomains. This coupling promotes recruitment and activation of the Rho-GTPase ROP6 in response to auxin, whereas disruption of VLCFA synthesis or sphingolipid composition disperses PS and ROP6 nanodomains, impairing cytoskeletal reorganization and directional growth. Our findings reveal interleaflet coupling as a fundamental organizing principle linking membrane asymmetry to signaling, providing a conceptual framework for spatial and temporal control of signal transduction across eukaryotic membranes.

plant biology↗

bioRxiv2020

Dimerization of the Mineralocorticoid Receptor LigandBinding Domain by helix 9, 10 and the F-domain

In vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear receptor (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to the group of oxo-steroidian NRs, together with the glucocorticoid (GR), progesterone (PR), and androgen (AR) receptors. Classically, these oxo-steroidian NRs homodimerize and bind to specific genomic sequences to activate gene expression. NRs are multi-domain proteins, and dimerization is mediated by both the DNA (DBD) and ligand binding (LBD) domains, with the latter thought to provide the largest dimerization interface. However, at the structural level, the LBD dimerization of oxo-steroidian receptors has remained largely a matter of debate. This is linked to the receptor refractory expression, purification and crystallization. As a result, there is currently no consensus on a common homodimer assembly across the 4 receptors, i.e. GR, PR, AR and MR, despite their sequence homology. Examining the available MR LBD crystals and using widely plebiscited tools such as PISA, PRISM and EPPIC, and the MM/PBSA method, we have determined that an interface mediated by the helices H9 and H10 of the LBD as well as by the F domain presents the features of a biological protein-protein interaction surface. This interface which has been observed in both GR and MR crystals, distinguished itself among other contacts and provided for the first time a homodimer architecture that is common to both oxo-steroidian receptors.

bioinformatics↗