Biology subjects

Fogeron, M.-L.

Publications and source records attributed to Fogeron, M.-L..

5 recordsLinked to original sources

bioRxiv2026

Residue-level predictions of the protein-protein interactions of the hepatitis B virus core and envelope proteins

We here predicted the interactions between the capsid (Cp) and envelope proteins (S/M/LHBs) of the hepatitis B virus using a recently established mutation-driven deep-learning model, as well as coevolution signatures that serve as markers of physical interactions and/or functional relationships. The sequence-based analyses reveal putative protein-protein interaction (PPI) hotspots in proteins, and identify abundant coevolved residues within and across proteins. We analyze the results with a focus on the intermolecular interactions between Cp and the large envelope protein LHBs, especially its disordered preS domain. We compare the predicted PPI interface sites to previous evidence on PPIs, derived from mutational analyses described in the literature. We equally integrate experimental NMR data that provide a rationale for the previous observation that spike-binding peptides inhibit core-envelope interactions. Our work sheds new light on the molecular mechanisms at play on HBV envelopment, and provides starting points for the experimental investigation of these interactions using structural and molecular virology approaches.

biophysics↗

bioRxiv2023

Do NSm virulence factors in the Bunyavirales order originate from Gn gene duplication?

One-third of the nine WHO shortlisted pathogens prioritized for research and development in public health emergencies belong to the Bunyavirales order. Several Bunyavirales species carry an NSm protein that acts as a virulence factor. We predicted the structures of these NSm protein and unexpectedly found that in two families, its cytosolic domain is inferred to have a similar fold to the cytosolic domain of the viral envelope-forming glycoprotein N (Gncyto) encoded on the same genome fragment. We show that although the sequence identity between the NSmcyto and Gncyto domains is low, the conservation of the two zinc finger-forming CCHC motifs explains the predicted structural conservation. Importantly, our predictions provide a first glimpse into the long unknown structure of NSm and its link to virulence. Also, these predictions suggest that NSm is the result of a gene duplication event in the Bunyavirales Nairoviridae and Peribunyaviridae families, and that such events may be common in the recent evolutionary history of RNA viruses.

bioinformatics↗

bioRxiv2022

Molecular elucidation of drug-induced abnormal assemblies of the Hepatitis B Virus capsid protein by solid-state NMR

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a new class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. We show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T=4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation.

biophysics↗

bioRxiv2021

Biomolecular solid-state NMR spectroscopy at highest field: the gain in resolution at 1200 MHz

Progress in NMR in general and in biomolecular applications in particular is driven by increasing magnetic-field strengths leading to improved resolution and sensitivity of the NMR spectra. Recently, persistent superconducting magnets at a magnetic field strength (magnetic induction) of 28.2 T corresponding to 1200 MHz proton resonance frequency became commercially available. We present here a collection of high-field NMR spectra of a variety of proteins, including molecular machines, membrane proteins and viral capsids and others. We show this large panel in order to provide an overview over a range of representative systems under study, rather than a single best performing model system. We discuss both carbon-13 and proton-detected experiments, and show that in 13C spectra substantially higher numbers of peaks can be resolved compared to 850 MHz while for 1H spectra the most impressive increase in resolution is observed for aliphatic side-chain resonances.

biophysics↗

bioRxiv2021

SARS-CoV-2 ORF7b: is a bat virus protein homologue a major cause of COVID-19 symptoms?

ORF7b is an accessory protein of SARS-CoV-2, the virus behind the COVID-19 pandemic. Using cell-free synthesized ORF7b, we experimentally show that ORF7b assembles into stable multimers. The ORF7b sequence shows a transmembrane segment, which multimerizes through a leucine zipper. We hypothesize that ORF7b has the potential to interfere with important cellular processes that involve leucine-zipper formation, and present two particularly striking examples. First, leucine zippers are central in heart rhythm regulation through multimerization of phospholamban in cardiomyocytes. Second, epithelial cell-cell adhesion relies on E-cadherins, which dimerize using a transmembrane leucine zipper. Most common symptoms of SARS-CoV-2 infection, including heart arrythmias, odor loss, impaired oxygen uptake and intestinal problems, up to multiorgan failure, can be rationalized by a possible interference of ORF7b with the functions of these proteins. We ask whether this is pure coincidence, or whether our observations point to disruption by ORF7b of vital processes in COVID-19.

biochemistry↗