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

Cappadocia, Laurant; Pichler, A.; Lima, Christopher D.

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons78508

Pichler, A.
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Cappadocia, L., Pichler, A., & Lima, C. D. (2015). Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase. Nature Structural & Molecular Biology, 22(12), 968-975.

Cite as: https://hdl.handle.net/someHandle/test/escidoc:902497

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.