CBFβ allosterically regulates the Runx1 Runt domain via a dynamic conformational equilibrium

J Yan, Y Liu, SM Lukasik, NA Speck… - Nature structural & …, 2004 - nature.com
J Yan, Y Liu, SM Lukasik, NA Speck, JH Bushweller
Nature structural & molecular biology, 2004nature.com
Core binding factors (CBFs) are heterodimeric transcription factors consisting of a DNA-
binding CBFα subunit and non-DNA-binding CBFβ subunit. The CBFβ subunit increases the
affinity of the DNA-binding Runt domain of CBFα for DNA while making no direct contacts to
the DNA. We present evidence for conformational exchange in the S-switch region in a Runt
domain–DNA complex that is quenched upon CBFβ binding. Analysis of 15N backbone
relaxation parameters shows that binding of CBFβ reduces the backbone dynamics in the …
Abstract
Core binding factors (CBFs) are heterodimeric transcription factors consisting of a DNA-binding CBFα subunit and non-DNA-binding CBFβ subunit. The CBFβ subunit increases the affinity of the DNA-binding Runt domain of CBFα for DNA while making no direct contacts to the DNA. We present evidence for conformational exchange in the S-switch region in a Runt domain–DNA complex that is quenched upon CBFβ binding. Analysis of 15N backbone relaxation parameters shows that binding of CBFβ reduces the backbone dynamics in the microsecond-to-millisecond time frame for several regions of the Runt domain that make energetically important contacts with the DNA. The DNA also undergoes conformational exchange in the Runt domain–DNA complex that is quenched in the presence of CBFβ. Our results indicate that allosteric regulation by the CBFβ subunit is mediated by a shift in an existing dynamic conformational equilibrium of both the Runt domain and DNA.
nature.com