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Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442243/ https://www.ncbi.nlm.nih.gov/pubmed/22842904 http://dx.doi.org/10.1038/nature11376 |
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author | Plechanovová, Anna Jaffray, Ellis Tatham, Michael H. Naismith, James H. Hay, Ronald T. |
author_facet | Plechanovová, Anna Jaffray, Ellis Tatham, Michael H. Naismith, James H. Hay, Ronald T. |
author_sort | Plechanovová, Anna |
collection | PubMed |
description | Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING of RNF4 in complex with E2 (UbcH5a) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The C-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilise the consequent tetrahedral transition state intermediate. |
format | Online Article Text |
id | pubmed-3442243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-34422432013-03-06 Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis Plechanovová, Anna Jaffray, Ellis Tatham, Michael H. Naismith, James H. Hay, Ronald T. Nature Article Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING of RNF4 in complex with E2 (UbcH5a) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The C-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilise the consequent tetrahedral transition state intermediate. 2012-09-06 /pmc/articles/PMC3442243/ /pubmed/22842904 http://dx.doi.org/10.1038/nature11376 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Plechanovová, Anna Jaffray, Ellis Tatham, Michael H. Naismith, James H. Hay, Ronald T. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title | Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title_full | Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title_fullStr | Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title_full_unstemmed | Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title_short | Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis |
title_sort | structure of a ring e3 ligase and ubiquitin-loaded e2 primed for catalysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442243/ https://www.ncbi.nlm.nih.gov/pubmed/22842904 http://dx.doi.org/10.1038/nature11376 |
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