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Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3
RING E3 ligases catalyze the transfer of ubiquitin (Ub) from E2 ubiquitin-conjugating enzyme thioesterified with Ub (E2~Ub) to substrate. For RING E3 dimers, the RING domain of one subunit and tail of the second cooperate to prime Ub, but how this is accomplished by monomeric RING E3s in the absence...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471106/ https://www.ncbi.nlm.nih.gov/pubmed/23851457 http://dx.doi.org/10.1038/nsmb.2621 |
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author | Dou, Hao Buetow, Lori Sibbet, Gary J. Cameron, Kenneth Huang, Danny T. |
author_facet | Dou, Hao Buetow, Lori Sibbet, Gary J. Cameron, Kenneth Huang, Danny T. |
author_sort | Dou, Hao |
collection | PubMed |
description | RING E3 ligases catalyze the transfer of ubiquitin (Ub) from E2 ubiquitin-conjugating enzyme thioesterified with Ub (E2~Ub) to substrate. For RING E3 dimers, the RING domain of one subunit and tail of the second cooperate to prime Ub, but how this is accomplished by monomeric RING E3s in the absence of a tail-like component is unknown. Here, we present a crystal structure of a monomeric RING E3, Tyr363-phosphorylated human CBL-B, bound to a stabilized Ub-linked E2, revealing a similar mechanism in activating E2~Ub. Both pTyr363 and the pTyr363-induced element interact directly with Ub’s Ile36 surface, improving the catalytic efficiency of Ub transfer by ~200-fold. Hence, interactions outside the canonical RING domain are crucial for optimizing Ub transfer in both monomeric and dimeric RING E3s. We propose that an additional non-RING Ub-priming element may be a common RING E3 feature. |
format | Online Article Text |
id | pubmed-4471106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44711062015-06-18 Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 Dou, Hao Buetow, Lori Sibbet, Gary J. Cameron, Kenneth Huang, Danny T. Nat Struct Mol Biol Article RING E3 ligases catalyze the transfer of ubiquitin (Ub) from E2 ubiquitin-conjugating enzyme thioesterified with Ub (E2~Ub) to substrate. For RING E3 dimers, the RING domain of one subunit and tail of the second cooperate to prime Ub, but how this is accomplished by monomeric RING E3s in the absence of a tail-like component is unknown. Here, we present a crystal structure of a monomeric RING E3, Tyr363-phosphorylated human CBL-B, bound to a stabilized Ub-linked E2, revealing a similar mechanism in activating E2~Ub. Both pTyr363 and the pTyr363-induced element interact directly with Ub’s Ile36 surface, improving the catalytic efficiency of Ub transfer by ~200-fold. Hence, interactions outside the canonical RING domain are crucial for optimizing Ub transfer in both monomeric and dimeric RING E3s. We propose that an additional non-RING Ub-priming element may be a common RING E3 feature. 2013-07-14 2013-08 /pmc/articles/PMC4471106/ /pubmed/23851457 http://dx.doi.org/10.1038/nsmb.2621 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 Dou, Hao Buetow, Lori Sibbet, Gary J. Cameron, Kenneth Huang, Danny T. Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title | Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title_full | Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title_fullStr | Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title_full_unstemmed | Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title_short | Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3 |
title_sort | essentiality of a non-ring element in priming donor ubiquitin for catalysis by a monomeric e3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471106/ https://www.ncbi.nlm.nih.gov/pubmed/23851457 http://dx.doi.org/10.1038/nsmb.2621 |
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