Non-covalent SUMO interactions with (de)conjugation enzymes

SUMOylation - a protein post-translational modification (PTM) related to ubiquitylation - involves the reversible covalent attachment of the small ubiquitin-like modifier (SUMO) to proteins. During the conjugation and deconjugation cycle, SUMO is recognised and positioned by various enzymes through specific non-covalent interactions. This review discusses the core interactions with the SAE2 subunit of the SUMOspecific heterodimeric E1 enzyme SAE1:SAE2, the SUMO E2 enzyme UBC9 and the SUMO-specific proteases of the SENP family and USPL1. We describe the evolutionary origins of these interactions and their structural basis; moreover, as SUMO:enzyme interactions are generally similar in their overall outline to those between ubiquitin and its specific enzymes, we highlight these similarities, as well as the differences. All of the mentioned interactions use a similar surface on SUMO, which is distinct from the groove that binds SUMO-interacting motifs (SIMs), meaning that while the enzyme interactions are mutually exclusive, each is compatible with simultaneous SIM binding. This review is accompanied by another in the same issue that focuses on interactions with SUMO E3 ligases and downstream effectors of SUMOylation, together providing comprehensive coverage of the non-covalent interactions formed by SUMO proteins.