Biology subjects

Antoine, R.

Publications and source records attributed to Antoine, R..

2 recordsLinked to original sources

bioRxiv2022

Post-transcriptional regulation by copper with a new upstream Open Reading Frame

Copper is essential to most living beings but also toxic. Bacteria have thus developed homeostatic mechanisms to tightly control its intracellular concentration. The 3-gene operon bp2923-bfrG-bp2921 is down-regulated by copper and notably encodes a TonB-dependent transporter in Bordetella pertussis. We show that the protein encoded by bp2923, which is a member of the DUF2946 family, represents a new type of upstream Open Reading Frame (uORF) involved in post-transcriptional regulation of the downstream genes. In the absence of copper, the entire operon is transcribed and translated. Perception of copper by the nascent bp2923-coded protein via its conserved CXXC motif triggers Rho-dependent transcription termination between the first and second genes by relieving translation arrest on a conserved C-terminal RAPP motif. Homologues of bp2923 are widespread in bacterial genomes, where they head operons predicted to participate in copper homeostasis. This work has unveiled an original mode of genetic regulation by a transition metal and identified a regulatory function for a member of an uncharacterized family of bacterial proteins that we have named CruR, for copper-responsive upstream regulator.

microbiology↗

bioRxiv2020

Templating S100A9 amyloids on Aβ fibrillar surfaces revealed by charge detection mass spectrometry, microscopy, kinetic and microfluidic analyses

The mechanism of amyloid co-aggregation and its nucleation process are not fully understood in spite of extensive studies. Deciphering the interactions between proinflammatory S100A9 protein and A{beta}42 peptide in Alzheimers disease is fundamental since inflammation plays a central role in the disease onset. Here we use innovative charge detection mass spectrometry (CDMS) together with biophysical techniques to provide mechanistic insight into the co-aggregation process and differentiate amyloid complexes at a single particle level. Combination of mass and charge distributions of amyloids together with reconstruction of the differences between them and detailed microscopy reveals that co-aggregation involves templating of S100A9 fibrils on the surface of A{beta}42 amyloids. Kinetic analysis further corroborates that the surfaces available for the A{beta}42 secondary nucleation are diminished due to the coating by S100A9 amyloids, while the binding of S100A9 to A{beta}42 fibrils is validated by a microfuidic assay. We demonstrate that synergy between CDMS, microscopy, kinetic and microfluidic analyses opens new directions in interdisciplinary research.

biophysics↗