title: DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending.
abstract: The Runt domain proteins are transcription regulators of major developmental pathways. Here we present the crystal structures of the Runt domain (RD) of the human protein RUNX1 and its DNA binding site in their free states and compare them with the published crystal structures of RD bound to DNA and to the partner protein CBFbeta. We demonstrate that (1) RD undergoes an allosteric transition upon DNA binding, which is further stabilized by CBFbeta, and that (2) the free DNA target adopts a bent-helical conformation compatible with that of the complex. These findings elucidate the mechanism by which CBFbeta enhances RD binding to DNA as well as the role of the intrinsic conformation of the DNA target in the recognition process.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartfeld
authors.forename: Linda
authors.initials: L
authors.lastname: Shimon
authors.forename: Graeme C
authors.initials: GC
authors.lastname: Couture
authors.forename: Dov
authors.initials: D
authors.lastname: Rabinovich
authors.forename: Felix
authors.initials: F
authors.lastname: Frolow
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
authors.forename: Zippora
authors.initials: Z
authors.lastname: Shakked
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D050676:Core Binding Factor Alpha 2 Subunit; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA