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Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains
The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951365/ https://www.ncbi.nlm.nih.gov/pubmed/20949063 http://dx.doi.org/10.1371/journal.pone.0013202 |
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author | Song, Ai-Xin Zhou, Chen-Jie Peng, Yu Gao, Xue-Chao Zhou, Zi-Ren Fu, Qing-Shan Hong, Jing Lin, Dong-Hai Hu, Hong-Yu |
author_facet | Song, Ai-Xin Zhou, Chen-Jie Peng, Yu Gao, Xue-Chao Zhou, Zi-Ren Fu, Qing-Shan Hong, Jing Lin, Dong-Hai Hu, Hong-Yu |
author_sort | Song, Ai-Xin |
collection | PubMed |
description | The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists of two α-helices and a flexible linker, whereas that of the Ub-bound form is much more compact with hydrophobic contacts between the two helices. NMR dynamics indicates that the flexible linker becomes rigid when AT3-UIM12 binds with Ub. Isothermal titration calorimetry and NMR titration demonstrate that AT3-UIM12 binds diUb with two distinct affinities, and the linker plays a critical role in association of the two helices in diUb binding. These results provide an implication that the tandem UIM12 interacts with Ub or diUb in a cooperative manner through an allosteric effect and dynamics change of the linker region, which might be related to its recognitions with various Ub chains and ubiquitinated substrates. |
format | Text |
id | pubmed-2951365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29513652010-10-14 Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains Song, Ai-Xin Zhou, Chen-Jie Peng, Yu Gao, Xue-Chao Zhou, Zi-Ren Fu, Qing-Shan Hong, Jing Lin, Dong-Hai Hu, Hong-Yu PLoS One Research Article The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists of two α-helices and a flexible linker, whereas that of the Ub-bound form is much more compact with hydrophobic contacts between the two helices. NMR dynamics indicates that the flexible linker becomes rigid when AT3-UIM12 binds with Ub. Isothermal titration calorimetry and NMR titration demonstrate that AT3-UIM12 binds diUb with two distinct affinities, and the linker plays a critical role in association of the two helices in diUb binding. These results provide an implication that the tandem UIM12 interacts with Ub or diUb in a cooperative manner through an allosteric effect and dynamics change of the linker region, which might be related to its recognitions with various Ub chains and ubiquitinated substrates. Public Library of Science 2010-10-07 /pmc/articles/PMC2951365/ /pubmed/20949063 http://dx.doi.org/10.1371/journal.pone.0013202 Text en Song et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Song, Ai-Xin Zhou, Chen-Jie Peng, Yu Gao, Xue-Chao Zhou, Zi-Ren Fu, Qing-Shan Hong, Jing Lin, Dong-Hai Hu, Hong-Yu Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title | Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title_full | Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title_fullStr | Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title_full_unstemmed | Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title_short | Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains |
title_sort | structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951365/ https://www.ncbi.nlm.nih.gov/pubmed/20949063 http://dx.doi.org/10.1371/journal.pone.0013202 |
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