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Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation
Human Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable f...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498358/ https://www.ncbi.nlm.nih.gov/pubmed/32710623 http://dx.doi.org/10.1093/nar/gkaa619 |
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author | Zhang, Jingfeng Fan, Jing-Song Li, Shuangli Yang, Yunhuang Sun, Peng Zhu, Qinjun Wang, Jiannan Jiang, Bin Yang, Daiwen Liu, Maili |
author_facet | Zhang, Jingfeng Fan, Jing-Song Li, Shuangli Yang, Yunhuang Sun, Peng Zhu, Qinjun Wang, Jiannan Jiang, Bin Yang, Daiwen Liu, Maili |
author_sort | Zhang, Jingfeng |
collection | PubMed |
description | Human Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable for YB-1 function. Until now, the roles of the C-terminal extension and phosphorylation in gene transcription and translation are still largely unknown. Here, we solved the structure of human YB-1 CSD with a C-terminal extension sequence (CSDex). The structure reveals that the extension interacts with several residues in the conventional CSD and adopts a rigid structure instead of being disordered. Either deletion of this extension or phosphorylation of S102 destabilizes the protein and results in partial unfolding. Structural characterization of CSDex in complex with a ssDNA heptamer shows that all the seven nucleotides are involved in DNA–protein interactions and the C-terminal extension provides a unique DNA binding site. Our DNA-binding study indicates that CSDex can recognize more DNA sequences than previously thought and the phosphorylation reduces its binding to ssDNA dramatically. Our results suggest that gene transcription and translation can be regulated by changing the affinity of CSDex binding to DNA and RNA through phosphorylation, respectively. |
format | Online Article Text |
id | pubmed-7498358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74983582020-09-23 Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation Zhang, Jingfeng Fan, Jing-Song Li, Shuangli Yang, Yunhuang Sun, Peng Zhu, Qinjun Wang, Jiannan Jiang, Bin Yang, Daiwen Liu, Maili Nucleic Acids Res Structural Biology Human Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable for YB-1 function. Until now, the roles of the C-terminal extension and phosphorylation in gene transcription and translation are still largely unknown. Here, we solved the structure of human YB-1 CSD with a C-terminal extension sequence (CSDex). The structure reveals that the extension interacts with several residues in the conventional CSD and adopts a rigid structure instead of being disordered. Either deletion of this extension or phosphorylation of S102 destabilizes the protein and results in partial unfolding. Structural characterization of CSDex in complex with a ssDNA heptamer shows that all the seven nucleotides are involved in DNA–protein interactions and the C-terminal extension provides a unique DNA binding site. Our DNA-binding study indicates that CSDex can recognize more DNA sequences than previously thought and the phosphorylation reduces its binding to ssDNA dramatically. Our results suggest that gene transcription and translation can be regulated by changing the affinity of CSDex binding to DNA and RNA through phosphorylation, respectively. Oxford University Press 2020-07-25 /pmc/articles/PMC7498358/ /pubmed/32710623 http://dx.doi.org/10.1093/nar/gkaa619 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Structural Biology Zhang, Jingfeng Fan, Jing-Song Li, Shuangli Yang, Yunhuang Sun, Peng Zhu, Qinjun Wang, Jiannan Jiang, Bin Yang, Daiwen Liu, Maili Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title | Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title_full | Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title_fullStr | Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title_full_unstemmed | Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title_short | Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation |
title_sort | structural basis of dna binding to human yb-1 cold shock domain regulated by phosphorylation |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498358/ https://www.ncbi.nlm.nih.gov/pubmed/32710623 http://dx.doi.org/10.1093/nar/gkaa619 |
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