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Structural Biology of Human H3K9 Methyltransferases
SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797608/ https://www.ncbi.nlm.nih.gov/pubmed/20084102 http://dx.doi.org/10.1371/journal.pone.0008570 |
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author | Wu, Hong Min, Jinrong Lunin, Vladimir V. Antoshenko, Tatiana Dombrovski, Ludmila Zeng, Hong Allali-Hassani, Abdellah Campagna-Slater, Valérie Vedadi, Masoud Arrowsmith, Cheryl H. Plotnikov, Alexander N. Schapira, Matthieu |
author_facet | Wu, Hong Min, Jinrong Lunin, Vladimir V. Antoshenko, Tatiana Dombrovski, Ludmila Zeng, Hong Allali-Hassani, Abdellah Campagna-Slater, Valérie Vedadi, Masoud Arrowsmith, Cheryl H. Plotnikov, Alexander N. Schapira, Matthieu |
author_sort | Wu, Hong |
collection | PubMed |
description | SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. |
format | Text |
id | pubmed-2797608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27976082010-01-16 Structural Biology of Human H3K9 Methyltransferases Wu, Hong Min, Jinrong Lunin, Vladimir V. Antoshenko, Tatiana Dombrovski, Ludmila Zeng, Hong Allali-Hassani, Abdellah Campagna-Slater, Valérie Vedadi, Masoud Arrowsmith, Cheryl H. Plotnikov, Alexander N. Schapira, Matthieu PLoS One Research Article SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. Public Library of Science 2010-01-11 /pmc/articles/PMC2797608/ /pubmed/20084102 http://dx.doi.org/10.1371/journal.pone.0008570 Text en Wu 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 Wu, Hong Min, Jinrong Lunin, Vladimir V. Antoshenko, Tatiana Dombrovski, Ludmila Zeng, Hong Allali-Hassani, Abdellah Campagna-Slater, Valérie Vedadi, Masoud Arrowsmith, Cheryl H. Plotnikov, Alexander N. Schapira, Matthieu Structural Biology of Human H3K9 Methyltransferases |
title | Structural Biology of Human H3K9 Methyltransferases |
title_full | Structural Biology of Human H3K9 Methyltransferases |
title_fullStr | Structural Biology of Human H3K9 Methyltransferases |
title_full_unstemmed | Structural Biology of Human H3K9 Methyltransferases |
title_short | Structural Biology of Human H3K9 Methyltransferases |
title_sort | structural biology of human h3k9 methyltransferases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797608/ https://www.ncbi.nlm.nih.gov/pubmed/20084102 http://dx.doi.org/10.1371/journal.pone.0008570 |
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