دورية أكاديمية
أعرض في EDS

UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.

التفاصيل البيبلوغرافية
العنوان: UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.
المؤلفون: Barnsby-Greer L; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Mabbitt PD; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK.; Scion, Rotorua, New Zealand., Dery MA; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Squair DR; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Wood NT; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Lamoliatte F; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Lange SM; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK., Virdee S; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, UK. s.s.virdee@dundee.ac.uk.
المصدر: Nature structural & molecular biology [Nat Struct Mol Biol] 2024 Feb; Vol. 31 (2), pp. 351-363. Date of Electronic Publication: 2024 Jan 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101186374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-9985 (Electronic) Linking ISSN: 15459985 NLM ISO Abbreviation: Nat Struct Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Nature Pub. Group, c2004-
مواضيع طبية MeSH: Ubiquitin-Protein Ligases*/metabolism , Ubiquitin-Conjugating Enzymes*/metabolism, Humans ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/metabolism ; Catalysis ; Ubiquitination ; Calmodulin-Binding Proteins/metabolism
مستخلص: UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a 'hemiRING' zinc finger, a helical-rich UBR zinc-finger interacting (UZI) subdomain, and an N-terminal region that can serve as an affinity factor for the E2 conjugating enzyme (E2). The structure of an E2-E3 complex provides atomic-level insight into the specificity determinants of the hemiRING toward the cognate E2s UBE2A/UBE2B. Via an allosteric mechanism, the UZI subdomain modestly activates the Ub-loaded E2 (E2∼Ub). We propose attenuated activation is complemented by the intrinsically high lysine reactivity of UBE2A, and their cooperation imparts a reactivity profile important for substrate specificity and optimal degradation kinetics. These findings reveal the mechanistic underpinnings of a neuronal N-degron E3, its specific recruitment of UBE2A, and highlight the underappreciated architectural diversity of cross-brace domains with Ub E3 activity.
(© 2024. The Author(s).)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MC_UU_00018/7 United Kingdom MRC_ Medical Research Council; MC_UU_12016/8 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
0 (Ubiquitin)
EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
EC 2.3.2.23 (UBE2A protein, human)
EC 2.3.2.23 (UBE2B protein, human)
EC 2.3.2.27 (UBR4 protein, human)
0 (Calmodulin-Binding Proteins)
تواريخ الأحداث: Date Created: 20240105 Date Completed: 20240219 Latest Revision: 20240320
رمز التحديث: 20240320
مُعرف محوري في PubMed: PMC10873205
DOI: 10.1038/s41594-023-01192-4
PMID: 38182926
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-9985
DOI:10.1038/s41594-023-01192-4