[HTML][HTML] Structural basis for the heterodimeric interaction between the acute leukaemia‐associated transcription factors AML1 and CBFβ

AJ Warren, J Bravo, RL Williams, TH Rabbitts - The EMBO journal, 2000 - embopress.org
The EMBO journal, 2000embopress.org
Mutations in the genes encoding the interacting proteins AML1 and CBFβ 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 CBFβ is essential for haematopoiesis. We report the 2.6 Å resolution crystal
structure of the complex between the AML1 Runt domain and CBFβ, which represents a
paradigm for the mode of interaction of this highly conserved family of transcription factors …
Abstract
Mutations in the genes encoding the interacting proteins AML1 and CBFβ 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 CBFβ is essential for haematopoiesis. We report the 2.6 Å resolution crystal structure of the complex between the AML1 Runt domain and CBFβ, 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 CBFβ in osteogenesis, and reveals a potential protein interaction platform composed of conserved negatively charged residues on the surface of CBFβ.
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