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

ABSTRACT: 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. SENP5, along with SENP3, are nucleolar proteins involved in ribosome biogenesis and preferentially target SUMO2/3 isoforms. Here, we present the crystal structures of human SENP5 in complex with both SUMO1 and SUMO2 isoforms. These structures reveal a minimal complex interface and elucidate the molecular basis for SENP5's preference for the SUMO2 isoform. This preference can be attributed to a basic patc

SUBMITTER: Sanchez-Alba L 

PROVIDER: S-EPMC12098989 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature