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Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase
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. In this paper, 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. Finally, our results are consistent with ZNF451 functioning as a bona fide SUMO E3 ligase.
- Sloan Kettering Inst., New York, NY (United States). Structural Biology Program
- Max Planck Inst. of Immunobiology and Epigenetics, Freiburg (Germany). Dept. of Epigenetics
- Sloan Kettering Inst., New York, NY (United States). Structural Biology Program. Howard Hughes Medical Inst.
- Publication Date:
- OSTI Identifier:
- Grant/Contract Number:
- AC02-06CH11357; P41RR012408; P41GM103473; P41 GM103403; S10 RR029205; GM065872; P30 CA008748; DFG-SPP1365 PI 917/2-1
- Accepted Manuscript
- Journal Name:
- Nature Structural & Molecular Biology
- Additional Journal Information:
- Journal Volume: 22; Journal Issue: 12; Journal ID: ISSN 1545-9993
- Nature Publishing Group
- Research Org:
- Sloan Kettering Inst., New York, NY (United States); Max Planck Inst. of Immunobiology and Epigenetics, Freiburg (Germany)
- Sponsoring Org:
- USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States); Max Planck Society (Germany); German Research Foundation (DFG)
- Country of Publication:
- United States
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Biochemistry; Structural biology; X-ray crystallography
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