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Structural basis for ubiquitylation by HOIL-1
The linear ubiquitin chain assembly complex synthesises linear Ub chains which constitute a binding and activation platform for components of the TNF signalling pathway. One of the components of LUBAC is the ubiquitin ligase HOIL-1 which has been shown to generate oxyester linkages on several protei...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853177/ https://www.ncbi.nlm.nih.gov/pubmed/36685275 http://dx.doi.org/10.3389/fmolb.2022.1098144 |
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author | Wu, Qilong Koliopoulos, Marios G. Rittinger, Katrin Stieglitz, Benjamin |
author_facet | Wu, Qilong Koliopoulos, Marios G. Rittinger, Katrin Stieglitz, Benjamin |
author_sort | Wu, Qilong |
collection | PubMed |
description | The linear ubiquitin chain assembly complex synthesises linear Ub chains which constitute a binding and activation platform for components of the TNF signalling pathway. One of the components of LUBAC is the ubiquitin ligase HOIL-1 which has been shown to generate oxyester linkages on several proteins and on linear polysaccharides. We show that HOIL-1 activity requires linear tetra-Ub binding which enables HOIL-1 to mono-ubiquitylate linear Ub chains and polysaccharides. Furthermore, we describe the crystal structure of a C-terminal tandem domain construct of HOIL-1 comprising the IBR and RING2 domains. Interestingly, the structure reveals a unique bi-nuclear Zn-cluster which substitutes the second zinc finger of the canonical RING2 fold. We identify the C-terminal histidine of this bi-nuclear Zn-cluster as the catalytic base required for the ubiquitylation activity of HOIL-1. Our study suggests that the unique zinc-coordinating architecture of RING2 provides a binding platform for ubiquitylation targets. |
format | Online Article Text |
id | pubmed-9853177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98531772023-01-21 Structural basis for ubiquitylation by HOIL-1 Wu, Qilong Koliopoulos, Marios G. Rittinger, Katrin Stieglitz, Benjamin Front Mol Biosci Molecular Biosciences The linear ubiquitin chain assembly complex synthesises linear Ub chains which constitute a binding and activation platform for components of the TNF signalling pathway. One of the components of LUBAC is the ubiquitin ligase HOIL-1 which has been shown to generate oxyester linkages on several proteins and on linear polysaccharides. We show that HOIL-1 activity requires linear tetra-Ub binding which enables HOIL-1 to mono-ubiquitylate linear Ub chains and polysaccharides. Furthermore, we describe the crystal structure of a C-terminal tandem domain construct of HOIL-1 comprising the IBR and RING2 domains. Interestingly, the structure reveals a unique bi-nuclear Zn-cluster which substitutes the second zinc finger of the canonical RING2 fold. We identify the C-terminal histidine of this bi-nuclear Zn-cluster as the catalytic base required for the ubiquitylation activity of HOIL-1. Our study suggests that the unique zinc-coordinating architecture of RING2 provides a binding platform for ubiquitylation targets. Frontiers Media S.A. 2023-01-06 /pmc/articles/PMC9853177/ /pubmed/36685275 http://dx.doi.org/10.3389/fmolb.2022.1098144 Text en Copyright © 2023 Wu, Koliopoulos, Rittinger and Stieglitz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Wu, Qilong Koliopoulos, Marios G. Rittinger, Katrin Stieglitz, Benjamin Structural basis for ubiquitylation by HOIL-1 |
title | Structural basis for ubiquitylation by HOIL-1 |
title_full | Structural basis for ubiquitylation by HOIL-1 |
title_fullStr | Structural basis for ubiquitylation by HOIL-1 |
title_full_unstemmed | Structural basis for ubiquitylation by HOIL-1 |
title_short | Structural basis for ubiquitylation by HOIL-1 |
title_sort | structural basis for ubiquitylation by hoil-1 |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853177/ https://www.ncbi.nlm.nih.gov/pubmed/36685275 http://dx.doi.org/10.3389/fmolb.2022.1098144 |
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