Skip to content

Research at St Andrews

Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin transfer

Research output: Contribution to journalArticlepeer-review

Author(s)

Paul Murphy, Yingqi Xu, Sarah L. Rouse, Ellis G Jaffray, Anna Plechanovova, Steve J. Matthews, Carlos Penedo, Ronald T. Hay

School/Research organisations

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.
Close

Details

Original languageEnglish
Article number3807
Number of pages13
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 30 Jul 2020

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition

    St-Pierre, P., Shaw, E. S., Jacques, S., Dalgarno, P. A., Perez Gonzalez, C., Picard-Jean, F., Penedo, C. & Lafontaine, D. A., 8 May 2021, (E-pub ahead of print) In: Nucleic Acids Research. Advance Article, 14 p.

    Research output: Contribution to journalArticlepeer-review

  2. The influence of various regions of the FOXP2 sequence on its structure and DNA binding function

    Thulo, M., Rabie, M. A., Pahad, N., Donald, H. L., Blane, A. A., Perumal, C. M., Penedo, C. & Fanucchi, S., Jan 2021, In: Bioscience Reports. 41, 1, 13 p., BSR20202128.

    Research output: Contribution to journalArticlepeer-review

  3. Ubiquitin transfer by a RING E3 ligase occurs from a closed E2~ubiquitin conformation

    Branigan, E., Penedo, C. & Hay, R. T., 5 Jun 2020, In: Nature Communications. 11, 11 p., 2846.

    Research output: Contribution to journalArticlepeer-review

  4. Asymmetric base-pair opening drives helicase unwinding dynamics

    Colizzi, F., Perez-Gonzalez, C., Fritzen, R., Levy, Y., White, M. F., Penedo, J. C. & Bussi, G., 5 Nov 2019, In: Proceedings of the National Academy of Sciences of the United States of America. 116, 45, p. 22471-22477 7 p.

    Research output: Contribution to journalArticlepeer-review

  5. Single molecule spectroscopy of polyfluorene chains reveals β-phase content and phase reversibility in organic solvents

    Brenlla, A., Tenopala-Carmona, F., Kanibolotsky, A. L., Skabara, P. J., Samuel, I. D. W. & Penedo-Esteiro, J. C., 9 Oct 2019, (E-pub ahead of print) In: Matter. In press

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. High Mountain Asian glacier response to climate revealed by multi-temporal satellite observations since the 1960s

    Bhattacharya, A., Bolch, T., Mukherjee, K., King, O. G. A., Kapitsa, V., Neckel, N. & Yao, T., 5 Jul 2021, In: Nature Communications. 12, 13 p., 4133.

    Research output: Contribution to journalArticlepeer-review

  2. The long lives of primates and the ‘invariant rate of ageing’ hypothesis

    Colchero, F., Aburto, J. M., Archie, E. A., Boesch, C., Breuer, T., Campos, F. A., Collins, A., Conde, D. A., Cords, M., Crockford, C., Thompson, M. E., Fedigan, L. M., Fichtel, C., Groenenberg, M., Hobaiter, C., Kappeler, P. M., Lawler, R. R., Lewis, R. J., Machanda, Z. P., Manguette, M. L. & 20 others, Muller, M. N., Packer, C., Parnell, R. J., Perry, S., Pusey, A. E., Robbins, M. M., Seyfarth, R. M., Silk, J. B., Staerk, J., Stoinski, T. S., Stokes, E. J., Strier, K. B., Strum, S. C., Tung, J., Villavicencio, F., Wittig, R. M., Wrangham, R. W., Zuberbühler, K., Vaupel, J. W. & Alberts, S. C., 16 Jun 2021, In: Nature Communications. 12, 10 p., 3666.

    Research output: Contribution to journalArticlepeer-review

  3. Real-time imaging of cellular forces using optical interference

    Meek, A. T., Kronenberg, N. M., Morton, A., Liehm, P., Murawski, J., Dalaka, E., Booth, J. H., Powis, S. J. & Gather, M. C., 11 Jun 2021, In: Nature Communications. 12, 11 p., 3552.

    Research output: Contribution to journalArticlepeer-review

  4. Crustal rejuvenation stabilised Earth’s first cratons

    Mulder, J. A., Nebel, O., Gardiner, N. J., Cawood, P. A., Wainwright, A. N. & Ivanic, T. J., 10 Jun 2021, In: Nature Communications. 12, 7 p., 3535 .

    Research output: Contribution to journalArticlepeer-review

  5. A first constraint on basal melt-water production of the Greenland ice sheet

    Karlsson, N. B., Solgaard, A. M., Mankoff, K. D., Gillet-Chaulet, F., MacGregor, J. A., Box, J. E., Citterio, M., Colgan, W. T., Larsen, S. H., Kjeldsen, K. K., Korsgaard, N. J., Benn, D. I., Hewitt, I. J. & Fausto, R. S., 8 Jun 2021, In: Nature Communications. 12, 3461.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Nature Communications (Journal)

    Ife Okafor-Yarwood (Reviewer)

    23 Mar 2020

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  2. Nature Communications (Journal)

    Andy Gardner (Reviewer)

    Feb 2018

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

ID: 269137377

Top