دورية أكاديمية
HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.
| العنوان: | HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain. |
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| المؤلفون: | Grabarczyk DB; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria. daniel.grabarczyk@imp.ac.at., Petrova OA; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Deszcz L; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Kurzbauer R; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Murphy P; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Ahel J; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Vogel A; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Gogova R; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Faas V; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Kordic D; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Schleiffer A; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Meinhart A; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Imre R; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Lehner A; Vienna Biocenter Core Facilities, Vienna BioCenter, Vienna, Austria., Neuhold J; Vienna Biocenter Core Facilities, Vienna BioCenter, Vienna, Austria., Bader G; Boehringer Ingelheim RCV, Vienna, Austria., Stolt-Bergner P; Boehringer Ingelheim RCV, Vienna, Austria., Böttcher J; Boehringer Ingelheim RCV, Vienna, Austria., Wolkerstorfer B; Boehringer Ingelheim RCV, Vienna, Austria., Fischer G; Boehringer Ingelheim RCV, Vienna, Austria., Grishkovskaya I; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Haselbach D; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Kessler D; Boehringer Ingelheim RCV, Vienna, Austria., Clausen T; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria. tim.clausen@imp.ac.at. |
| المصدر: | Nature chemical biology [Nat Chem Biol] 2021 Oct; Vol. 17 (10), pp. 1084-1092. Date of Electronic Publication: 2021 Jul 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101231976 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4469 (Electronic) Linking ISSN: 15524450 NLM ISO Abbreviation: Nat Chem Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Group, [2005]- |
| مواضيع طبية MeSH: | Caenorhabditis elegans Proteins/*metabolism , Microsporidia/*metabolism , Ubiquitin-Protein Ligases/*metabolism, Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/chemistry ; Caenorhabditis elegans Proteins/genetics ; Fungal Proteins ; Insecta ; Microsporidia/genetics ; Models, Molecular ; Protein Conformation ; Protein Domains ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitin-Protein Ligases/genetics |
| مستخلص: | HUWE1 is a universal quality-control E3 ligase that marks diverse client proteins for proteasomal degradation. Although the giant HECT enzyme is an essential component of the ubiquitin-proteasome system closely linked with severe human diseases, its molecular mechanism is little understood. Here, we present the crystal structure of Nematocida HUWE1, revealing how a single E3 enzyme has specificity for a multitude of unrelated substrates. The protein adopts a remarkable snake-like structure, where the C-terminal HECT domain heads an extended alpha-solenoid body that coils in on itself and houses various protein-protein interaction modules. Our integrative structural analysis shows that this ring structure is highly dynamic, enabling the flexible HECT domain to reach protein targets presented by the various acceptor sites. Together, our data demonstrate how HUWE1 is regulated by its unique structure, adapting a promiscuous E3 ligase to selectively target unassembled orphan proteins. (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| التعليقات: | Comment in: Nat Chem Biol. 2021 Oct;17(10):1014-1015. (PMID: 34345051) |
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| معلومات مُعتمدة: | 694978 International ERC_ European Research Council; F 7905 Austria FWF_ Austrian Science Fund FWF |
| المشرفين على المادة: | 0 (Caenorhabditis elegans Proteins) 0 (Fungal Proteins) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20210723 Date Completed: 20211012 Latest Revision: 20221030 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7611724 |
| DOI: | 10.1038/s41589-021-00831-5 |
| PMID: | 34294896 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1552-4469 |
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| DOI: | 10.1038/s41589-021-00831-5 |