SUMObinding

Sumo binding refers to the recognition and interaction between proteins and SUMO, a small ubiquitin-like modifier that can be covalently attached to target proteins in a process called SUMOylation. SUMO-binding is typically non-covalent and mediated by specific motifs and domains that recognize SUMO or SUMO-conjugated substrates.

A primary mechanism for SUMO binding is through SUMO-interacting motifs, or SIMs. SIMs are short, often hydrophobic sequences that dock into a complementary hydrophobic surface on SUMO. The interaction is usually modest in affinity and can be regulated by nearby post-translational modifications, such as phosphorylation, which modulate binding strength and specificity. In addition to SIMs, other protein domains can contribute to SUMO binding in particular contexts, including UBA-like or other specialized motifs found in certain SUMO-binding proteins.

SUMO-binding proteins participate in a wide range of cellular processes by recognizing SUMOylated substrates or SUMO chains. They can recruit chromatin modifiers and transcriptional regulators to SUMOylated promoters, participate in DNA repair and genome stability, or influence subcellular localization and protein turnover. A notable example is the SUMO-targeted ubiquitin ligase RNF4, which binds poly-SUMO chains via SIMs to ubiquitinate SUMOylated substrates, linking SUMOylation to ubiquitin-mediated outcomes.

Techniques to study SUMO binding include affinity pull-downs, SUMO overlay assays, yeast two-hybrid approaches, and mass spectrometry-based proteomics. Understanding SUMO binding clarifies how SUMOylation shapes protein interaction networks and cellular responses.