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SUMO-activated target traps (SATTs) enable the identification of a comprehensive E3-specific SUMO proteome

2023; American Association for the Advancement of Science; Volume: 9; Issue: 31 Linguagem: Inglês

10.1126/sciadv.adh2073

2375-2548

Daniel Salas‐Lloret, Nicolette S. Jansen, Easa Nagamalleswari, Coen van der Meulen, Ekaterina Gracheva, Arnoud H. de Ru, H. Anne Marie Otte, Peter A. van Veelen, Andrea Pichler, Joachim Goedhart, Alfred C.O. Vertegaal, Román González‐Prieto,

Glycosylation and Glycoproteins Research

Ubiquitin and ubiquitin-like conjugation cascades consist of dedicated E1, E2, and E3 enzymes with E3s providing substrate specificity. Mass spectrometry-based approaches have enabled the identification of more than 6500 SUMO2/3 target proteins. The limited number of SUMO E3s provides the unique opportunity to systematically study E3 substrate wiring. We developed SUMO-activated target traps (SATTs) and systematically identified substrates for eight different SUMO E3s, PIAS1, PIAS2, PIAS3, PIAS4, NSMCE2, ZNF451, LAZSUL (ZNF451-3), and ZMIZ2. SATTs enabled us to identify 427 SUMO1 and 961 SUMO2/3 targets in an E3-specific manner. We found pronounced E3 substrate preference. Quantitative proteomics enabled us to measure substrate specificity of E3s, quantified using the SATT index. Furthermore, we developed the Polar SATTs web-based tool to browse the dataset in an interactive manner. Overall, we uncover E3-to-target wiring of 1388 SUMO substrates, highlighting unique and overlapping sets of substrates for eight different SUMO E3 ligases.