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TitleThe linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateJun 18, 2021
AuthorsAlan Rodriguez Carvajal / Irina Grishkovskaya / Carlos Gomez Diaz / Antonia Vogel / Adar Sonn-Segev / Manish S Kushwah / Katrin Schodl / Luiza Deszcz / Zsuzsanna Orban-Nemeth / Shinji Sakamoto / Karl Mechtler / Philipp Kukura / Tim Clausen / David Haselbach / Fumiyo Ikeda /
PubMed AbstractThe linear ubiquitin chain assembly complex (LUBAC) is the only known ubiquitin ligase for linear/Met1-linked ubiquitin chain formation. One of the LUBAC components, heme-oxidized IRP2 ubiquitin ...The linear ubiquitin chain assembly complex (LUBAC) is the only known ubiquitin ligase for linear/Met1-linked ubiquitin chain formation. One of the LUBAC components, heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L), was recently shown to catalyse oxyester bond formation between ubiquitin and some substrates. However, oxyester bond formation in the context of LUBAC has not been directly observed. Here, we present the first 3D reconstruction of human LUBAC obtained by electron microscopy and report its generation of heterotypic ubiquitin chains containing linear linkages with oxyester-linked branches. We found that this event depends on HOIL-1L catalytic activity. By cross-linking mass spectrometry showing proximity between the catalytic RING-in-between-RING (RBR) domains, a coordinated ubiquitin relay mechanism between the HOIL-1-interacting protein (HOIP) and HOIL-1L ligases is suggested. In mouse embryonic fibroblasts, these heterotypic chains were induced by TNF, which is reduced in cells expressing an HOIL-1L catalytic inactive mutant. In conclusion, we demonstrate that LUBAC assembles heterotypic ubiquitin chains by the concerted action of HOIP and HOIL-1L.
External linksElife / PubMed:34142657 / PubMed Central
MethodsEM (single particle)
Resolution17.0 Å
Structure data

EMDB-11054:
Linear Ubiquitin Chain Assembly Complex
Method: EM (single particle) / Resolution: 17.0 Å

Source
  • Homo sapiens (human)

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