Structural analyses of DNA recognition by the AML1/Runx-1 runt domain and its allosteric control by CBFβ

Tahir H. Tahirov; Taiko Inoue-Bungo; Hisayuki Morii; Atsushi Fujikawa; Motoko Sasaki; Kazumi Kimura; Masaaki Shiina; Ko Sato; Takashi Kumasaka; Masaki Yamamoto; Shunsuke Ishii; Kazuhiro Ogata

doi:10.1016/S0092-8674(01)00271-9

Structural analyses of DNA recognition by the AML1/Runx-1 runt domain and its allosteric control by CBFβ

Tahir H. Tahirov, Taiko Inoue-Bungo, Hisayuki Morii, Atsushi Fujikawa, Motoko Sasaki, Kazumi Kimura, Masaaki Shiina, Ko Sato, Takashi Kumasaka, Masaki Yamamoto, Shunsuke Ishii, Kazuhiro Ogata

Research output: Contribution to journal › Article › peer-review

154 Scopus citations

Abstract

The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2α/Runx and CBFβ/PEBP2β subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBFα(Runt domain)-CBFβ(core domain)-C/EBPβ(bZip)-DNA, AML1/Runx-1/CBFα(Runt domain)-C/EBPβ(bZip)-DNA, and AML1/Runx-1/CBFα(Runt domain)-DNA complexes. The hydrogen bonding network formed among CBFα(Runt domain) and CBFβ, and CBFα(Runt domain) and DNA revealed the allosteric regulation mechanism of CBFα(Runt domain)-DNA binding by CBFβ. The point mutations of CBFα related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.

Original language	English (US)
Pages (from-to)	755-767
Number of pages	13
Journal	Cell
Volume	104
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(01)00271-9
State	Published - Mar 9 2001
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/S0092-8674(01)00271-9

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@article{de6fcda474014d4e8fc441e1e8119068,

title = "Structural analyses of DNA recognition by the AML1/Runx-1 runt domain and its allosteric control by CBFβ",

abstract = "The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2α/Runx and CBFβ/PEBP2β subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBFα(Runt domain)-CBFβ(core domain)-C/EBPβ(bZip)-DNA, AML1/Runx-1/CBFα(Runt domain)-C/EBPβ(bZip)-DNA, and AML1/Runx-1/CBFα(Runt domain)-DNA complexes. The hydrogen bonding network formed among CBFα(Runt domain) and CBFβ, and CBFα(Runt domain) and DNA revealed the allosteric regulation mechanism of CBFα(Runt domain)-DNA binding by CBFβ. The point mutations of CBFα related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.",

author = "Tahirov, {Tahir H.} and Taiko Inoue-Bungo and Hisayuki Morii and Atsushi Fujikawa and Motoko Sasaki and Kazumi Kimura and Masaaki Shiina and Ko Sato and Takashi Kumasaka and Masaki Yamamoto and Shunsuke Ishii and Kazuhiro Ogata",

note = "Funding Information: We thank S. Akira for NF-IL6 cDNA and N. Kamiya, Y. Kawano, T. Kato, I. Aoki, and M. Hosaka for their generous support. We also thank M. Oda for preliminary experiments and helpful comments on ITC studies. This research was supported in part by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST) to K. O. ",

year = "2001",

month = mar,

day = "9",

doi = "10.1016/S0092-8674(01)00271-9",

language = "English (US)",

volume = "104",

pages = "755--767",

journal = "Cell",

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number = "5",

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TY - JOUR

T1 - Structural analyses of DNA recognition by the AML1/Runx-1 runt domain and its allosteric control by CBFβ

AU - Tahirov, Tahir H.

AU - Inoue-Bungo, Taiko

AU - Morii, Hisayuki

AU - Fujikawa, Atsushi

AU - Sasaki, Motoko

AU - Kimura, Kazumi

AU - Shiina, Masaaki

AU - Sato, Ko

AU - Kumasaka, Takashi

AU - Yamamoto, Masaki

AU - Ishii, Shunsuke

AU - Ogata, Kazuhiro

N1 - Funding Information: We thank S. Akira for NF-IL6 cDNA and N. Kamiya, Y. Kawano, T. Kato, I. Aoki, and M. Hosaka for their generous support. We also thank M. Oda for preliminary experiments and helpful comments on ITC studies. This research was supported in part by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST) to K. O.

PY - 2001/3/9

Y1 - 2001/3/9

N2 - The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2α/Runx and CBFβ/PEBP2β subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBFα(Runt domain)-CBFβ(core domain)-C/EBPβ(bZip)-DNA, AML1/Runx-1/CBFα(Runt domain)-C/EBPβ(bZip)-DNA, and AML1/Runx-1/CBFα(Runt domain)-DNA complexes. The hydrogen bonding network formed among CBFα(Runt domain) and CBFβ, and CBFα(Runt domain) and DNA revealed the allosteric regulation mechanism of CBFα(Runt domain)-DNA binding by CBFβ. The point mutations of CBFα related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.

AB - The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2α/Runx and CBFβ/PEBP2β subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBFα(Runt domain)-CBFβ(core domain)-C/EBPβ(bZip)-DNA, AML1/Runx-1/CBFα(Runt domain)-C/EBPβ(bZip)-DNA, and AML1/Runx-1/CBFα(Runt domain)-DNA complexes. The hydrogen bonding network formed among CBFα(Runt domain) and CBFβ, and CBFα(Runt domain) and DNA revealed the allosteric regulation mechanism of CBFα(Runt domain)-DNA binding by CBFβ. The point mutations of CBFα related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.

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JO - Cell

JF - Cell

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ER -

Structural analyses of DNA recognition by the AML1/Runx-1 runt domain and its allosteric control by CBFβ

Abstract

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