Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-17647-x
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Funding
- Wellcome Trust Investigator Awards [098391/Z/12/Z, 217196/Z/19/Z]
- Cancer Research UK [C434/A21747]
- Wellcome Trust Studentship [109113/Z/15/Z]
- Wellcome Trust [215539, 104833]
- Scottish Universities Physics Alliance (SUPA)
- University of St. Andrews
- Wellcome Trust [109113/Z/15/Z, 098391/Z/12/Z, 217196/Z/19/Z] Funding Source: Wellcome Trust
- MRC [MR/P028225/1] Funding Source: UKRI
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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 similar to 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.
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