Deciphering the specificity of the human SUMO protease, SENP5
New work from the Protein Structure Group, led by David Reverter, in collaboration with researchers from Leiden University and IDIBAPS.
Post-translational modifications are changes in proteins that play a fundamental role in cellular regulation, as they can alter their biological activity, influencing various physiological processes. Among them is SUMOylation, a mechanism in which the SUMO (Small Ubiquitin-like MOdifier) ¿¿protein covalently binds to other proteins, modulating their functions. It is a complex process in which a large number of proteins participate, both those necessary for SUMO activation and those that are the target of the modification. It is important to highlight the role of SUMO proteases, responsible for activating the SUMO molecule, as well as processing and eliminating its binding to target proteins.
Our research group has carried out the structural characterization of the human protease SENP5 with the aim of identifying the key residues for the discrimination and specificity of SENP5 with respect to the different types of SUMO.
In this article we present the three-dimensional structure of SENP5 in complex with different types of SUMO. The results of the analysis of the different complexes reveal a positively charged region that is directly involved in the preference of SENP5 for SUMO2. Thanks to the structural characterization we have been able to define the key contacts of SENP5 with SUMO2, opening the way to the investigation and design of possible specific inhibitors for this protease.
This work has been carried out by the research group of Dr. David Reverter, researcher of the Institute of Biotechnology and Biomedicine and the Department of Biochemistry and Molecular Biology of the UAB, in collaboration with the group of Dr. Monique Mulder, linked to the University of Leiden (Netherlands) and with the group of Dr. Virginia Amador, IDIBAPS (Barcelona).
The scientific work has been published in the journal Nature Communications. Sánchez-Alba, L., Ying, L., Maletic, M.D. et al. Structural basis for the human SENP5’s SUMO isoform discrimination. Nat Commun 16, 4764 (2025). https://doi.org/10.1038/s41467-025-60029-4.