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The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains.
Rodriguez Carvajal, Alan; Grishkovskaya, Irina; Gomez Diaz, Carlos; Vogel, Antonia; Sonn-Segev, Adar; Kushwah, Manish S; Schodl, Katrin; Deszcz, Luiza; Orban-Nemeth, Zsuzsanna; Sakamoto, Shinji; Mechtler, Karl; Kukura, Philipp; Clausen, Tim; Haselbach, David; Ikeda, Fumiyo.
Afiliación
  • Rodriguez Carvajal A; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Grishkovskaya I; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Gomez Diaz C; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Vogel A; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Sonn-Segev A; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United Kingdom.
  • Kushwah MS; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United Kingdom.
  • Schodl K; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Deszcz L; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Orban-Nemeth Z; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Sakamoto S; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Mechtler K; Pharmaceutical Frontier Research Labs, JT Inc., Yokohama, Japan.
  • Kukura P; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Clausen T; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United Kingdom.
  • Haselbach D; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • Ikeda F; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
Elife ; 102021 06 18.
Article en En | MEDLINE | ID: mdl-34142657
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Ubiquitina / Ubiquitina-Proteína Ligasas Límite: Animals / Female / Humans / Male Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Ubiquitina / Ubiquitina-Proteína Ligasas Límite: Animals / Female / Humans / Male Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido