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

被引：213

作者：

Tahirov, TH

Inoue-Bungo, T

Morii, H

Fujikawa, A

Sasaki, M

Kimura, K

Shiina, M

Sato, K

Kumasaka, T

Yamamoto, M

Ishii, S

Ogata, K

机构：

[1] Yokohama City Univ, Sch Med, Kanagawa Acad Sci & Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Yokohama City Univ, Sch Med, Dept Biol Struct, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[3] Yokohama City Univ, Sch Med, Dept Urol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[4] Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[5] Yokohama City Univ, Sch Med, Dept Biochem, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[6] Natl Inst Biosci & Human Technol, Prot Folding Grp, Tsukuba, Ibaraki 3058566, Japan

[7] RIKEN, Harima Inst SPring 8, Biocrystallog Technol Div, Sayo, Hyogo 6795148, Japan

[8] RIKEN, Harima Inst SPring 8, Struct Biophys Lab, Sayo, Hyogo 6795148, Japan

[9] JST, Res Project, CREST, Tsukuba, Ibaraki 3050074, Japan

[10] RIKEN, Tsukuba Inst, Genet Mol Lab, Tsukuba, Ibaraki 3050074, Japan

来源：

CELL | 2001年 / 104卷 / 05期

关键词：

D O I：

10.1016/S0092-8674(01)00271-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBPSalpha/Runx and CBF beta /PEBP2 beta 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/CBF alpha (Runt domain)-CBF beta (core domain)-C/EBP beta (b-Zip)-DNA, AML1/Runx-1/CBF alpha (Runt domain)-C/EBP beta (bZip)-DNA, and AML1/Runx-1/CBF alpha (Runt domain)DNA complexes. The hydrogen bonding network formed among CBF alpha (Runt domain) and CBF beta, and CBF alpha (Runt domain) and DNA revealed the allosteric regulation mechanism of CBF alpha (Runt domain)-DNA binding by CBF beta. The point mutations of CBF alpha related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.

引用

页码：755 / 767

页数：13

共 58 条

[1] A simple screening for mutant DNA binding proteins: Application to murine transcription factor PEBP2 alpha subunit, a founding member of the Runt domain protein family [J].