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Structural basis for the heterodimeric interaction between the acute leukaemia‐associated transcription factors AML1 and CBFβ
Author(s) -
Warren Alan J.,
Bravo Jerónimo,
Williams Roger L.,
Rabbitts Terence H.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.12.3004
Subject(s) - biology , gene , transcription factor , point mutation , genetics , computational biology , mutation , microbiology and biotechnology
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.