Typologie d'actualités: Team Molecular, Structural and Chemical Biology

Marcin Suskiewicz, research fellow at the CBM, obtained an ERC Starting 2022 grant

SUMOylation is a natural reaction that changes the structure of proteins in cells. Thanks to his ERC SUMOwriteNread project, Marcin Suskiewicz of the CBM wants to characterize the mechanism by which it occurs, as well as its effects on the properties of proteins. This reaction remains poorly understood even though it probably plays an essential role in our cells.

Find out more on the CNRS Institute of Chemistry website

CBM PhD students have talent!

Ons Kharrat, from the "NMR of Biomolecules" group, received one of the 3 prizes for the best oral communication at the GDR MuFoPAM days which took place from October 19 to 21, 2022.
This prize was awarded to him by the company Genepep (https://www.genepep.com/accueil/).

Elodie Villalonga, from the "Cell signaling and neurofibromatosis" group, won one of the 2 prizes for the best oral communication
and
Valentin Beauvais, from the group “Dysregulation of autophagy during inflammation due to HIV”, received one of the poster prizes at the 34th Biotechnocentre conference which took place on October 20 and 21, 2022.

A major advance in the understanding of DNA damage repair

The "DNA repair: structure, function and dynamics" team has just revealed, in the prestigious journal Nucleic Acid Research, how archaeal DNA glycosylases are able to recognize and repair, at the molecular level, certain lesions in their DNA.

To know more :
Structural and functional determinants of the archaeal 8-oxoguanine-DNA glycosylase AGOG for DNA damage recognition and processing
Coste Franck, Goffinont Stéphane, Cros Julien, Gaudon Virginie, Guérin Martine, Garnier Norbert, Confalonieri Fabrice, Flament Didier, Suskiewicz Marcin Josef, Castaing Bertrand https://doi.org/10.1093/nar/gkac932

Identification of a ‘double‘ protein post-translational modification

Proteins are the main ‘molecular machines’ of the cell. To efficiently perform their tasks, they have to be dynamically switched on and off, recruited to specific cellular locations, and degraded in a timely manner. One of the main mechanisms that regulate these processes is temporary covalent attachment, to a protein, of extra regulatory elements known as protein post-translational modifications. The modification reaction is catalysed by specific enzymes and can lead to changes in protein activity, localisation, or half-life. Two of the common protein modifications are ubiquitin and ADP-ribose, each of which can be linked directly to a protein substrate.

In the study published in Science Advances, an international team of researchers, including Vincent Aucagne, Marcin Suskiewicz, and Hervé Meudal from the CBM in Orléans, led by Ivan Ahel and Dragana Ahel groups at the University of Oxford, have demonstrated that these two individual modifications can be joined together, producing a ‘double’ protein modification. The enzymes responsible for this process are DELTEX E3 ligases, which can efficiently attach ubiquitin to protein-linked ADP-ribose. A key contribution of Orléans scientists to the project was the analysis of the ubiquitin-ADP-ribose linkage performed using mass spectrometry (MS) and nuclear magnetic resonance (NMR) equipment of the new MOV2ING platform in Orléans.

The study shows that different protein modifications can be joined together to either combine two regulatory signals or produce a third, distinct signal, with a specific function. This shows previously unappreciated level of complexity in protein regulation.

While the role of ubiquitin-ADP-ribose in cells remains unclear, DELTEX enzymes have previously been linked to both development and antiviral response. The authors showed that the SARS-CoV-2 virus possesses enzymes that can remove the new modification, possibly allowing the virus to inhibit the host immune response.

References :
Kang Zhu, Marcin J. Suskiewicz, Hloušek-Kasun, Hervé Meudal, Andreja Mikoč, Vincent Aucagne, Dragana Ahel and Ivan Ahel
DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on protein substrates
Science Advances, 5 Oct 2022, Vol 8, Issue 40 DOI: 10.1126/sciadv.add4253

A versatile new approach to seek constitutive or conditional helicase substrates at global scale

Helicases are ubiquitous ‘molecular motor’ enzymes that disrupt nucleic acid (NA) helices and NA-protein interactions. Despite the key roles of helicases in many cellular processes and diseases, their target repertoires and the determinants of their functional specialization are often unknown. Scientists from the ‘RNA remodeling’ group of CBM have developed a new screening scheme, Helicase-SELEX, to elucidate helicase substrate requirements and find natural or synthetic helicase substrates in large NA sequence libraries. Using the transcription termination Rho helicase as prototype, the CBM scientists have discovered ~3300 functional substrate sequences in Escherichia coli, thereby providing the first detailed map of Rho utilization (Rut) sites at genome scale. Further, they have shown that inclusion of a Rho cofactor (NusG) in the selection scheme can modulate the H-SELEX outcome and help probe specificity determinants at global scale. Finally, they have used H-SELEX to evolve synthetic Rut sequences operating as riboswitches able to elicit Rho activity in vitro and in vivo only in presence of an orthogonal cofactor (serotonin). Thus, Helicase-SELEX is a versatile new approach to characterize or exploit helicases for fundamental or biotechnology purposes.

The CNRS Institute of Chemistry has reported this new original screening approach on its website

Référence

Delaleau M., Eveno E., Simon I., Schwartz A & Boudvillain M.
A scalable framework for the discovery of functional helicase substrates and helicase-driven regulatory switches
PNAS 2022

https://www.pnas.org/doi/10.1073/pnas.2209608119

7th Biotechnocentre theme day – June 17, 2022

Researchers in biosciences and life chemistry met "face-to-face" for the Biotechnocentre's thematic day on "Exposome and Epigenetics: how does the environment play with our genes?" ". Renowned speakers declined the different facets of the exposome: physical or chemical exposure or exposure to different pathogens, stress, diet, social inequalities... They also highlighted the impact of the exposome on the environment and on our health, which can have different consequences depending on gender, age, genetic heritage and on its regulation by reversible epigenetic modifications.
See the Booklet of the day (poster, program, summaries).