Structural Analyses of DNA Recognition by the AML1/Runx-1 Runt Domain and Its Allosteric Control by CBFβ

Autor: Motoko Sasaki, Tahir H. Tahirov, Ko Sato, Taiko Inoue-Bungo, Masaaki Shiina, Takashi Kumasaka, Atsushi Fujikawa, Masaki Yamamoto, S. Ishhi, Kazumi Kimura, Kazuhiro Ogata, Hisayuki Morii
Rok vydání: 2001
Předmět:
Core Binding Factor alpha Subunits
Magnetic Resonance Spectroscopy
Core Binding Factor beta Subunit
Cell
Molecular Sequence Data
Allosteric regulation
Computational biology
Calorimetry
Biology
Crystallography
X-Ray
Core binding factor
medicine.disease_cause
Protein Structure
Secondary
General Biochemistry
Genetics and Molecular Biology
Mice
chemistry.chemical_compound
Allosteric Regulation
Proto-Oncogene Proteins
hemic and lymphatic diseases
medicine
Animals
Amino Acid Sequence
Transcription factor
Dna recognition
Genetics
Mutation
Leukemia
Biochemistry
Genetics and Molecular Biology(all)
Point mutation
DNA
Molecular biology
Protein Structure
Tertiary
DNA-Binding Proteins
medicine.anatomical_structure
Transcription Factor AP-2
chemistry
Runt domain
Mutagenesis
Core Binding Factor Alpha 2 Subunit
Dimerization
Protein Binding
Transcription Factors
Zdroj: Scopus-Elsevier
ISSN: 0092-8674
Popis: The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2alpha/Runx and CBFbeta/PEBP2beta 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/CBFalpha(Runt domain)-CBFbeta(core domain)-C/EBPbeta(bZip)-DNA, AML1/Runx-1/CBFalpha(Runt domain)-C/EBPbeta(bZip)-DNA, and AML1/Runx-1/CBFalpha(Runt domain)-DNA complexes. The hydrogen bonding network formed among CBFalpha(Runt domain) and CBFbeta, and CBFalpha(Runt domain) and DNA revealed the allosteric regulation mechanism of CBFalpha(Runt domain)-DNA binding by CBFbeta. The point mutations of CBFalpha related to the aforementioned diseases were also mapped and their effect on DNA binding is discussed.
Databáze: OpenAIRE
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