Interaction networks of SIM-binding groove mutants reveal alternate modes of SUMO binding and profound impact on SUMO conjugation.

ABSTRACT: The best-characterized mode of noncovalent SUMO interaction involves binding of a SUMO-interaction motif (SIM) to a conserved binding groove in SUMO. Our knowledge on other types of SUMO interactions is still limited. Using SIM-binding groove SUMO2/3 mutants and mass spectrometry, we identified proteins that bind to SUMO in an alternate manner. Domain-enrichment analysis characterized a group of WD40 repeat domain-containing proteins as SIM-independent SUMO interactors, and we validated direct binding of SEC13 and SEH1L to SUMO in vitro. Using AlphaFold-3 modeling and in vitro mutational analysis, we identified residues in the WD40 domain of SEC13 and SUMO2/3's C terminus involved in the interaction. Furthermore, SIM-binding groove mutants failed to interact with SUMO E3 ligases bel

SUBMITTER: Claessens LA 

PROVIDER: S-EPMC12077520 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature