Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin transfer
| Autor: | Ellis Jaffray, Steve Matthews, Anna Plechanovová, Paul Murphy, Yingqi Xu, Ronald T. Hay, Sarah L. Rouse, J. Carlos Penedo |
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| Přispěvatelé: | University of St Andrews. School of Physics and Astronomy, University of St Andrews. Centre for Biophotonics, University of St Andrews. Biomedical Sciences Research Complex |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Ubiquitylation QH301 Biology Science Ubiquitin-Protein Ligases General Physics and Astronomy QH426 Genetics General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences QH301 0302 clinical medicine Ubiquitin Protein Domains Humans lcsh:Science Protein secondary structure QH426 R2C chemistry.chemical_classification DNA ligase Multidisciplinary biology RNF4 Chemistry Ubiquitination Substrate (chemistry) Nuclear Proteins DAS General Chemistry Molecular conformation Ubiquitin ligase Intrinsically Disordered Proteins 030104 developmental biology Domain (ring theory) Enzyme mechanisms Biophysics biology.protein Small Ubiquitin-Related Modifier Proteins lcsh:Q BDC Solution-state NMR 030217 neurology & neurosurgery Function (biology) Protein Binding Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2041-1723 |
| Popis: | The human genome contains an estimated 600 ubiquitin E3 ligases, many of which are single-subunit E3s (ssE3s) that can bind to both substrate and ubiquitin-loaded E2 (E2~Ub). Within ssE3s structural disorder tends to be located in substrate binding and domain linking regions. RNF4 is a ssE3 ligase with a C-terminal RING domain and disordered N-terminal region containing SUMO Interactions Motifs (SIMs) required to bind SUMO modified substrates. Here we show that, although the N-terminal region of RNF4 bears no secondary structure, it maintains a compact global architecture primed for SUMO interaction. Segregated charged regions within the RNF4 N-terminus promote compaction, juxtaposing RING domain and SIMs to facilitate substrate ubiquitination. Mutations that induce a more extended shape reduce ubiquitination activity. Our result offer insight into a key step in substrate ubiquitination by a member of the largest ubiquitin ligase subtype and reveal how a defined architecture within a disordered region contributes to E3 ligase function. RNF4 is a prototypical single-subunit E3 enzyme that can bind both substrate and ubiquitin-loaded E2. Here, the authors show that the RNF4 N-terminal region, although lacking a defined secondary structure, maintains a compact global conformation to facilitate ubiquitin transfer to the substrate. |
| Databáze: | OpenAIRE |
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