Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor

Abstract Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is...

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Autores principales:	Xiangkai Zhen, Bowen Li, Fen Hu, Shufeng Yan, Gabriele Meloni, Huiliang Li, Ning Shi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b6e4e83ed74743899d7bf5d8ab1f5acf
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spelling	oai:doaj.org-article:b6e4e83ed74743899d7bf5d8ab1f5acf2021-12-02T16:06:20ZCrystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor10.1038/s41598-017-03768-92045-2322https://doaj.org/article/b6e4e83ed74743899d7bf5d8ab1f5acf2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03768-9https://doaj.org/toc/2045-2322Abstract Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel β-sheets with 7 main strands, packing against each other, forming a β-sandwich. Compared to its homolog, Ndt80, MyRF has a smaller and less complex DBD lacking the helices and the big loops outside the core. Structural alignment reveals that MyRF DBD possess less interaction sites with DNA than Ndt80 and may bind only at the major groove of DNA. Moreover, the structure reveals a trimeric assembly, agreeing with the previous report that MyRF DBD functions as a trimer. The mutant that we designed based on the structure disturbed trimer formation, but didn’t affect the auto-cleavage reaction. It demonstrates that the activation of self-cleavage reaction of MyRF is independent of the presence of its N-terminal DBD homotrimer. The structure reported here will help to understand the molecular mechanism underlying the important roles of MyRF in myelin formation and development.Xiangkai ZhenBowen LiFen HuShufeng YanGabriele MeloniHuiliang LiNing ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiangkai Zhen Bowen Li Fen Hu Shufeng Yan Gabriele Meloni Huiliang Li Ning Shi Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
description	Abstract Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel β-sheets with 7 main strands, packing against each other, forming a β-sandwich. Compared to its homolog, Ndt80, MyRF has a smaller and less complex DBD lacking the helices and the big loops outside the core. Structural alignment reveals that MyRF DBD possess less interaction sites with DNA than Ndt80 and may bind only at the major groove of DNA. Moreover, the structure reveals a trimeric assembly, agreeing with the previous report that MyRF DBD functions as a trimer. The mutant that we designed based on the structure disturbed trimer formation, but didn’t affect the auto-cleavage reaction. It demonstrates that the activation of self-cleavage reaction of MyRF is independent of the presence of its N-terminal DBD homotrimer. The structure reported here will help to understand the molecular mechanism underlying the important roles of MyRF in myelin formation and development.
format	article
author	Xiangkai Zhen Bowen Li Fen Hu Shufeng Yan Gabriele Meloni Huiliang Li Ning Shi
author_facet	Xiangkai Zhen Bowen Li Fen Hu Shufeng Yan Gabriele Meloni Huiliang Li Ning Shi
author_sort	Xiangkai Zhen
title	Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
title_short	Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
title_full	Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
title_fullStr	Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
title_full_unstemmed	Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
title_sort	crystal structure of the dna-binding domain of myelin-gene regulatory factor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b6e4e83ed74743899d7bf5d8ab1f5acf
work_keys_str_mv	AT xiangkaizhen crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT bowenli crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT fenhu crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT shufengyan crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT gabrielemeloni crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT huiliangli crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor AT ningshi crystalstructureofthednabindingdomainofmyelingeneregulatoryfactor
_version_	1718385048674107392

Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor

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