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: | Journal article |
| Language: | English |
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eLife Sciences Publications
2021
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| _version_ | 1797056301121929216 |
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| author | Rodriguez Carvajal, A Grishkovskaya, I Gomez Diaz, C Vogel, A Sonn-Segev, A Kushwah, MS Schodl, K Deszcz, L Orban-Nemeth, Z Sakamoto, S Mechtler, K Kukura, P Clausen, T Haselbach, D Ikeda, F |
| author_facet | Rodriguez Carvajal, A Grishkovskaya, I Gomez Diaz, C Vogel, A Sonn-Segev, A Kushwah, MS Schodl, K Deszcz, L Orban-Nemeth, Z Sakamoto, S Mechtler, K Kukura, P Clausen, T Haselbach, D Ikeda, F |
| author_sort | Rodriguez Carvajal, A |
| collection | OXFORD |
| 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 | 2024-03-06T19:21:27Z |
| format | Journal article |
| id | oxford-uuid:1a3b45cd-8fb6-46a1-a938-b52a96ff3a3a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:21:27Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:1a3b45cd-8fb6-46a1-a938-b52a96ff3a3a2022-03-26T10:53:40ZThe linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chainsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1a3b45cd-8fb6-46a1-a938-b52a96ff3a3aEnglishSymplectic ElementseLife Sciences Publications2021Rodriguez Carvajal, AGrishkovskaya, IGomez Diaz, CVogel, ASonn-Segev, AKushwah, MSSchodl, KDeszcz, LOrban-Nemeth, ZSakamoto, SMechtler, KKukura, PClausen, THaselbach, DIkeda, FThe 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. |
| spellingShingle | Rodriguez Carvajal, A Grishkovskaya, I Gomez Diaz, C Vogel, A Sonn-Segev, A Kushwah, MS Schodl, K Deszcz, L Orban-Nemeth, Z Sakamoto, S Mechtler, K Kukura, P Clausen, T Haselbach, D Ikeda, F The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains |
| 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 |
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