Synthesis and Application of SUMO-Based Probes for SUMO Protease Profiling.

SUMOylation is a post-translation modification responsible for the regulation of many nuclear processes. Dysregulation can lead to various diseases, so the discovery of the mechanisms and players behind the (de)SUMOylation cycle is crucial. Here, we describe a linear SPPS approach to obtain SUMO2/3-based activity probes and their application in assessing the activity of deSUMOylases, ultimately aiding in the identification of small molecules that target this system.

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains.

Regulation by ubiquitin depends on E3 ligases forging chains of specific topologies, yet the mechanisms underlying the generation of atypical linkages remain largely elusive. Here we utilize biochemistry, chemistry, and cryo-EM to define the catalytic architecture producing K29 linkages and K29/K48 branches for the human HECT E3 TRIP12. TRIP12 resembles a pincer.

Structural basis for the human SENP5's SUMO isoform discrimination.

Post-translational SUMO modification is a widespread mechanism for regulating protein function within cells. In humans, SUMO-conjugated proteins are partially regulated by the deconjugating activity of six SENP family members. The proteolytic activity of these enzymes resides within a conserved catalytic domain that exhibits specificity for the two primary SUMO isoforms: SUMO1 and SUMO2/3.