The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains
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 sub...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/60660 |
| _version_ | 1811252901845139456 |
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| author | Alan 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 |
| author_facet | Alan 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 |
| author_sort | Alan Rodriguez Carvajal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:42:30Z |
| format | Article |
| id | doaj.art-9ec73005ec624671b20ef8eae113b8a2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:42:30Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9ec73005ec624671b20ef8eae113b8a22022-12-22T03:24:44ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.60660The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chainsAlan Rodriguez Carvajal0https://orcid.org/0000-0002-8340-8620Irina Grishkovskaya1Carlos Gomez Diaz2https://orcid.org/0000-0002-6416-806XAntonia Vogel3Adar Sonn-Segev4Manish S Kushwah5Katrin Schodl6Luiza Deszcz7Zsuzsanna Orban-Nemeth8Shinji Sakamoto9https://orcid.org/0000-0003-2480-2940Karl Mechtler10Philipp Kukura11Tim Clausen12https://orcid.org/0000-0003-1582-6924David Haselbach13https://orcid.org/0000-0002-5276-5633Fumiyo Ikeda14https://orcid.org/0000-0003-0407-2768Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaDepartment of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United KingdomDepartment of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United KingdomInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, AustriaInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaPharmaceutical Frontier Research Labs, JT Inc., Yokohama, JapanResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaDepartment of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United KingdomResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria; Medical Institute of Bioregulation (MIB), Kyushu University, Fukuoka, JapanThe 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.https://elifesciences.org/articles/60660E3 ubiquitin ligaseHOIL-1Loxyester-bond linkageRBRubiquitin |
| spellingShingle | Alan 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 The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains eLife E3 ubiquitin ligase HOIL-1L oxyester-bond linkage RBR ubiquitin |
| title | The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| title_full | The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| title_fullStr | The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| title_full_unstemmed | The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| title_short | The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| title_sort | linear ubiquitin chain assembly complex lubac generates heterotypic ubiquitin chains |
| topic | E3 ubiquitin ligase HOIL-1L oxyester-bond linkage RBR ubiquitin |
| url | https://elifesciences.org/articles/60660 |
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