التفاصيل البيبلوغرافية
| العنوان: |
NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly |
| المؤلفون: |
David T. Krist, Kheewoong Baek, Gary Kleiger, Lisa-Marie Neumaier, Maren Klügel, J. Rajan Prabu, Susanne von Gronau, Spencer Hill, Brenda A. Schulman |
| المصدر: |
Nature |
| سنة النشر: |
2020 |
| مصطلحات موضوعية: |
Models, Molecular, NEDD8 Protein, Protein Conformation, Ubiquitin-Protein Ligases, macromolecular substances, NEDD8, Article, Substrate Specificity, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Ubiquitin, NF-KappaB Inhibitor alpha, Humans, Phosphorylation, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, DNA ligase, Multidisciplinary, biology, fungi, Cryoelectron Microscopy, Ubiquitination, Active site, Ubiquitin ligase, Cell biology, chemistry, Ubiquitin-Conjugating Enzymes, biology.protein, Biocatalysis, 030217 neurology & neurosurgery, Cullin |
| الوصف: |
Eukaryotic cell biology depends on cullin-RING E3 ligase (CRL)-catalysed protein ubiquitylation(1), which is tightly controlled by the modification of cullin with the ubiquitin-like protein NEDD8(2-6). However, how CRLs catalyse ubiquitylation, and the basis of NEDD8 activation, remain unknown. Here we report the cryo-electron microscopy structure of a chemically trapped complex that represents the ubiquitylation intermediate, in which the neddylated CRL1(beta-TRCP) promotes the transfer of ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D to its recruited substrate, phosphorylated I kappa B alpha. NEDD8 acts as a nexus that binds disparate cullin elements and the RING-activated ubiquitin-linked UBE2D. Local structural remodelling of NEDD8 and large-scale movements of CRL domains converge to juxtapose the substrate and the ubiquitylation active site. These findings explain how a distinctive ubiquitin-like protein alters the functions of its targets, and show how numerous NEDD8-dependent interprotein interactions and conformational changes synergistically configure a catalytic CRL architecture that is both robust, to enable rapid ubiquitylation of the substrate, and fragile, to enable the subsequent functions of cullin-RING proteins. A cryo-electron microscopy structure provides insights into the activation of cullin-RING E3 ligases by NEDD8 and the consequent catalysis of ubiquitylation reactions. |
| وصف الملف: |
application/pdf |
| تدمد: |
0028-0836 |
| DOI: |
10.1038/s41586-020-2000-y |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07fe84e71915b67a0d43ed84d6cf20c1 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....07fe84e71915b67a0d43ed84d6cf20c1 |
| قاعدة البيانات: |
OpenAIRE |