Structural basis for role of ring finger protein RNF168 RING domain
| العنوان: | Structural basis for role of ring finger protein RNF168 RING domain |
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| المؤلفون: | Jie Chen, Minhao Wu, Aloysius Wilfred Raj Arokiaraj, Jianye Zang, Yue Tao, Huakai Wu, Weichang Zhang, Michael S.Y. Huen, Chengliang Wang, Xiaoqin Zhang |
| المصدر: | Cell Cycle. 12:312-321 |
| بيانات النشر: | Informa UK Limited, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Models, Molecular, Protein Conformation, Ubiquitin-Protein Ligases, chemistry.chemical_compound, Ubiquitin, Report, Ring finger, medicine, Humans, DNA Breaks, Double-Stranded, Cloning, Molecular, Molecular Biology, chemistry.chemical_classification, DNA ligase, biology, Cell Biology, Chromatin, Ubiquitin ligase, DNA-Binding Proteins, RING finger domain, medicine.anatomical_structure, Histone, Microscopy, Fluorescence, chemistry, Biochemistry, Ubiquitin-Conjugating Enzymes, biology.protein, Biophysics, Crystallization, RING Finger Domains, DNA, Developmental Biology |
| الوصف: | Ubiquitin adducts surrounding DNA double-strand breaks (DSBs) have emerged as molecular platforms important for the assembly of DNA damage mediator and repair proteins. Central to these chromatin modifications lies the E2 UBC13, which has been implicated in a bipartite role in priming and amplifying lys63-linked ubiquitin chains on histone molecules through coupling with the E3 RNF8 and RNF168. However, unlike the RNF8-UBC13 holoenyzme, exactly how RNF168 work in concert with UBC13 remains obscure. To provide a structural perspective for the RNF168-UBC13 complex, we solved the crystal structure of the RNF168 RING domain. Interestingly, while the RNF168 RING adopts a typical RING finger fold with two zinc ions coordinated by several conserved cystine and histine residues arranged in a C3HC4 “cross-brace” manner, structural superimposition of RNF168 RING with other UBC13-binding E3 ubiquitin ligases revealed substantial differences at its corresponding UBC13-binding interface. Consistently, and in stark contrast to that between RNF8 and UBC13, RNF168 did not stably associate with UBC13 in vitro or in vivo. Moreover, domain-swapping experiments indicated that the RNF8 and RNF168 RING domains are not functionally interchangeable. We propose that RNF8 and RNF168 operate in different modes with their cognate E2 UBC13 at DSBs. |
| تدمد: | 1551-4005 1538-4101 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::686a9e6eeb7d9405fbf639ef710bb3a1Test https://doi.org/10.4161/cc.23104Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....686a9e6eeb7d9405fbf639ef710bb3a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15514005 15384101 |
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