Structural insights into the SUMOylation reaction

30 June 2023 par Isabelle Frapart
The new study focussed on the process known as SUMOylation, an essential biological regulatory mechanism, inaugurates the "SUMOwriteNread" project funded by the European Research Council, which aims to crack secrets of SUMOylation.

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 -

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