Typologie d'actualités: Group DNA repair: Structure, Function and Dynamic

Comprehensive review about the “logic of protein modifications”

Among the main functional building blocks of living cells are proteins, small “molecular machines” produced by the cell according to the information encoded in genes. Each protein has its characteristic chemical composition which defines its structure and function.

In some circumstances, the chemical composition of a protein can be changed in an enzymatic process known as post-translational modification (PTM), whereby additional chemical groups are covalently attached to the protein. PTMs are used by the cell as a regulatory mechanism to control protein function. The addition of new chemical groups – which can come in different shapes and sizes, ranging from small groups, through sugars and lipids, to small proteins – changes the structure and interactions of a protein and can impact almost any aspect of its function.

Marcin Suskiewicz, a structural biologist and biochemist from the CBM, has devoted many years to studying various types of protein PTMs and currently supervises a project devoted to one particular type of PTMs, protein SUMOylation.

In the review published in the journal BioEssays, he reviews the history of the research into protein PTMs as well as various facets of this phenomenon, including the underlying chemical principles, molecular mechanisms, and evolution.

The review combines an introduction to the field with an overview of the recent literature and new ideas and hypotheses.

References:

The logic of protein post-translational modifications (PTMs): Chemistry, mechanisms and evolution of protein regulation through covalent attachments
Marcin Suskiewicz
BioEssays
First published:21 January 2024
https://doi-org.insb.bib.cnrs.fr/10.1002/bies.202300178

A review on ADP-ribosylation appeared in the journal Cell

ADP-ribosylation is a biochemical reaction in which the ADP-ribose group from NAD+ becomes covalently attached to various substrates. As such, ADP-ribosylation represents a ubiquitous modification of proteins and other biomolecules (e.g., nucleic acids). Catalysed by a range of specific enzymes, the most important of which in humans is PARP1, ADP-ribosylation serves as a regulatory mechanism influencing a wide array of cellular processes in all domains of life. This new review, published in the authoritative Leading Edge series of reviews of the journal Cell, covers the state of the art on this subject spanning structural biology, biochemistry, cell biology, and the clinical facets of ADP-ribosylation. In addition to Marcin Suskiewicz from the CBM as the first author, the review was co-authored by Ivan Ahel and members of his group at the University of Oxford.

Suskiewicz M., Prokhlrova E., Rack J.G.M., Ahel I.
ADP-ribosylation from molecular mechanisms to therapeutic implications
Cell Review, Volume 186, Issue 21, pages 4475-4495, October 12, 2023 - doi: 10.1016/j.cell.2023.08.03

The CNRS Institute of Chemistry reports on its website the work of CBM researchers

Understanding the function of proteins requires knowing their structures.
To do this, scientists used artificial intelligence to predict the shape of a class of "PARP" type proteins that regulate DNA repair, gene transcription, and antiviral response, but are also potential targets for new cancer therapies. This approach, published in the journal Nucleic Acids Research, could be extended to many other families of proteins.

Voir l'actualité sur le site de l'Institut de Chimie du CNRS

Référence

Updated protein domain annotation of the PARP protein family sheds new light on biological function
Marcin J. Suskiewicz, Deeksha Munnur, Øyvind Strømland, Ji-Chun Yang, Laura E. Easton, Chatrin Chatri , Kang Zhu, Domagoj Baretić, Stéphane Goffinont, Marion Schuller, Wing-Fung Wu, Jonathan M Elkins, Dragana Ahel, Sumana Sanyal, David Neuhaus & Ivan Ahel
Journal Nucleic Acids Research

https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad514/7199335?login=true

Structural insights into the SUMOylation reaction

SUMOylation and ubiquitylation are related protein modifications where small proteins (SUMO or ubiquitin) become covalently attached to protein substrates to regulate their function. Both these protein modifications are essential for viability and are strongly implicated in human disease, but SUMOylation remains less studied than ubiquitylation. A key step in both SUMOylation and ubiquitylation reactions is the formation of a reactive thioester molecule in which SUMO or ubiquitin becomes linked to a cysteine residue on proteins called E2. It is from there that SUMO/ubiquitin is transferred onto the final protein substrate. In the study just published in Journal of Biological Chemistry, the researchers from the CBM used site-directed mutagenesis to create a version of the human E2-SUMO thioester that – unlike the native reactive thioester – is chemically stable and can be studied with structural biology methods. The crystal structure of this molecule revealed potential regulatory mechanisms for the SUMOylation process. The mutagenesis approach was inspired by a method developed for the yeast SUMOylation pathway by the group of Chris Lima.

The article, authored by the CBM engineer Stéphane Goffinont and other members of the team “Protein Post-Translational Modifications and DNA Repair: Structure, Function, and Dynamics”, is the first publication from the project “SUMOwriteNread”. The project is led by the CBM researcher Marcin J. Suskiewicz and funded by the Horizon Europe programme of the European Union (European Research Council Starting Grant no 101078837).

Stéphane Goffinont, Franck Coste, Pierre Prieu-Serandon, Lucija Mance, Virginie Gaudon, Norbert Garnier, Bertrand Castaing and Marcin Józef Suskiewicz
Structural insights into the regulation of the human E2∼SUMO conjugate through analysis of its stable mimetic.
Journal of Biological Chemistry, Volume 299, Issue 7, 2023, 104870 - https://www.sciencedirect.com/science/article/pii/S0021925823018987