DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending.
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.
Bartfeld
Deborah
D
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Shimon
Linda
L
Couture
Graeme C
GC
Rabinovich
Dov
D
Frolow
Felix
F
Levanon
Ditsa
D
Groner
Yoram
Y
Shakked
Zippora
Z
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*
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA