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

Eisenhardt, N. et al. (2015) A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly. Nature Structural and Molecular Biology, 22(12), pp. 959-967. (doi: 10.1038/nsmb.3114) (PMID:26524493)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Chaugule, Dr Viduth
• Authors: Eisenhardt, N., Chaugule, V. K., Koidl, S., Droescher, M., Dogan, E., Rettich, J., Sutinen, P., Imanishi, S. Y., Hofmann, K., Palvimo, J. J., and Pichler, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nature Structural and Molecular Biology
• Publisher: Nature Publishing Group
• ISSN: 1545-9993
• ISSN (Online): 1545-9985