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Structural Studies of a Four-MBT Repeat Protein MBTD1
BACKGROUND: The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-c...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747274/ https://www.ncbi.nlm.nih.gov/pubmed/19841675 http://dx.doi.org/10.1371/journal.pone.0007274 |
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author | Eryilmaz, Jitka Pan, Patricia Amaya, Maria F. Allali-Hassani, Abdellah Dong, Aiping Adams-Cioaba, Melanie A. MacKenzie, Farrell Vedadi, Masoud Min, Jinrong |
author_facet | Eryilmaz, Jitka Pan, Patricia Amaya, Maria F. Allali-Hassani, Abdellah Dong, Aiping Adams-Cioaba, Melanie A. MacKenzie, Farrell Vedadi, Masoud Min, Jinrong |
author_sort | Eryilmaz, Jitka |
collection | PubMed |
description | BACKGROUND: The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of MBTD1 (residues 130–566aa covering the 4 MBT repeats) at 2.5 Å resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a “cavity insertion recognition mode” to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation. CONCLUSIONS: The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage. 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-2747274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27472742009-10-20 Structural Studies of a Four-MBT Repeat Protein MBTD1 Eryilmaz, Jitka Pan, Patricia Amaya, Maria F. Allali-Hassani, Abdellah Dong, Aiping Adams-Cioaba, Melanie A. MacKenzie, Farrell Vedadi, Masoud Min, Jinrong PLoS One Research Article BACKGROUND: The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of MBTD1 (residues 130–566aa covering the 4 MBT repeats) at 2.5 Å resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a “cavity insertion recognition mode” to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation. CONCLUSIONS: The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage. 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 2009-10-20 /pmc/articles/PMC2747274/ /pubmed/19841675 http://dx.doi.org/10.1371/journal.pone.0007274 Text en Eryilmaz 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 Eryilmaz, Jitka Pan, Patricia Amaya, Maria F. Allali-Hassani, Abdellah Dong, Aiping Adams-Cioaba, Melanie A. MacKenzie, Farrell Vedadi, Masoud Min, Jinrong Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title | Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title_full | Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title_fullStr | Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title_full_unstemmed | Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title_short | Structural Studies of a Four-MBT Repeat Protein MBTD1 |
title_sort | structural studies of a four-mbt repeat protein mbtd1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747274/ https://www.ncbi.nlm.nih.gov/pubmed/19841675 http://dx.doi.org/10.1371/journal.pone.0007274 |
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