A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly

  • Nat Struct Mol Biol. 2015 Dec;22(12):959-67. doi: 10.1038/nsmb.3114.
Nathalie Eisenhardt  1 ,  Viduth K Chaugule  1 ,  Stefanie Koidl  1 ,  Mathias Droescher  1 ,  Esen Dogan  1 ,  Jan Rettich  1 ,  Päivi Sutinen  2 ,  Susumu Y Imanishi  3 ,  Kay Hofmann  4 ,  Jorma J Palvimo  2 ,  Andrea Pichler  1
Affiliations
  • 1. Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
  • 2. Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
  • 3. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
  • 4. Institute for Genetics, University of Cologne, Cologne, Germany.
PMID: 26524493 DOI: 10.1038/nsmb.3114
Abstract

SUMO chains act as stress-induced degradation tags or repair factor-recruiting signals at DNA lesions. Although E1 activating, E2 conjugating and E3 ligating Enzymes efficiently assemble SUMO chains, specific chain-elongation mechanisms are unknown. E4 elongases are specialized E3 Ligases that extend a chain but are inefficient in the initial conjugation of the modifier. We identified ZNF451, a representative member of a new class of SUMO2 and SUMO3 (SUMO2/3)-specific Enzymes that execute catalysis via a tandem SUMO-interaction motif (SIM) region. One SIM positions the donor SUMO while a second SIM binds SUMO on the back side of the E2 enzyme. This tandem-SIM region is sufficient to extend a back side-anchored SUMO chain (E4 elongase activity), whereas efficient chain initiation also requires a zinc-finger region to recruit the initial acceptor SUMO (E3 Ligase activity). Finally, we describe four human proteins sharing E4 elongase activities and their function in stress-induced SUMO2/3 conjugation.