Projects per year
Abstract
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.
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.
Original language | English |
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Article number | 3807 |
Number of pages | 13 |
Journal | Nature Communications |
Volume | 11 |
Early online date | 30 Jul 2020 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- Enzyme mechanisms
- Molecular conformation
- Solution-state NMR
- Ubiquitylation
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Projects
- 2 Finished
-
Wellcome Trust PhD Studentship
Cuschieri, A., Keatch, R., Owen-Hughes, T. & Ryan, R.
1/09/15 → 31/08/19
Project: Research