Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFβ
Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFβ
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DOI：
10.1093/emboj/19.12.3004
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发表时间：
2000-06-15
期刊：
影响因子：
11.4
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Warren, AJ;Bravo, J;Rabbitts, TH
编码相互作用蛋白AML1和CBFβ的基因突变是急性白血病最常见的遗传异常，相关AML3基因的先天性突变与成骨障碍有关。此外，AML1与CBFβ的相互作用对造血是必不可少的。我们报道了AML1 Run结构域与CBFPβ之间的复合体的2.6埃分辨率晶体结构，这代表了这个高度保守的转录因子家族相互作用模式的范例。该结构表明与锁骨颅骨发育不良相关的点突变映射到保守的异二聚体界面，表明CBFPβ在成骨中发挥作用，并揭示了CBFβ表面由保守的负电荷残基组成的潜在蛋白质相互作用平台。
Mutations in the genes encoding the interacting proteins AML1 and CBF beta are the most common genetic abnormalities in acute leukaemia, and congenital mutations in the related AML3 gene are associated with disorders of osteogenesis. Furthermore, the interaction of AML1 with CBF beta is essential for haematopoiesis. We report the 2.6 Angstrom resolution crystal structure of the complex between the AML1 Runt domain and CBFP beta, which represents a paradigm for the mode of interaction of this highly conserved family of transcription factors. The structure demonstrates that point mutations associated with cleidocranial dysplasia map to the conserved heterodimer interface, suggesting a role for CBFP beta in osteogenesis, and reveals a potential protein interaction platform composed of conserved negatively charged residues on the surface of CBF beta.