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Nat Struct Mol Biol. 2015 Dec;22(12):968-75. doi: 10.1038/nsmb.3116. Epub 2015 Nov 2.

Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase.

Author information

1
Structural Biology Program, Sloan Kettering Institute, New York, New York, USA.
2
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
3
Howard Hughes Medical Institute, Sloan Kettering Institute, New York, New York, USA.

Abstract

E3 protein ligases enhance transfer of ubiquitin-like (Ubl) proteins from E2 conjugating enzymes to substrates by stabilizing the thioester-charged E2~Ubl in a closed configuration optimally aligned for nucleophilic attack. Here, we report biochemical and structural data that define the N-terminal domain of the Homo sapiens ZNF451 as the catalytic module for SUMO E3 ligase activity. The ZNF451 catalytic module contains tandem SUMO-interaction motifs (SIMs) bridged by a Pro-Leu-Arg-Pro (PLRP) motif. The first SIM and PLRP motif engage thioester-charged E2~SUMO while the next SIM binds a second molecule of SUMO bound to the back side of E2. We show that ZNF451 is SUMO2 specific and that SUMO modification of ZNF451 may contribute to activity by providing a second molecule of SUMO that interacts with E2. Our results are consistent with ZNF451 functioning as a bona fide SUMO E3 ligase.

PMID:
26524494
PMCID:
PMC4709122
DOI:
10.1038/nsmb.3116
[Indexed for MEDLINE]
Free PMC Article

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