2. Academic Validation
  3. A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly

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

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.

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