[PDF][PDF] The Ig fold of the core binding factor α Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains
MJ Berardi, C Sun, M Zehr, F Abildgaard, J Peng… - Structure, 1999 - cell.com
MJ Berardi, C Sun, M Zehr, F Abildgaard, J Peng, NA Speck, JH Bushweller
Structure, 1999•cell.comBackground: CBFA is the DNA-binding subunit of the transcription factor complex called
core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality
and a profound block in hematopoietic development. Chromosomal disruptions of the
human CBFA gene are associated with a large percentage of human leukemias. Results:
Utilizing nuclear magnetic resonance spectroscopy we have determined the three-
dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s …
core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality
and a profound block in hematopoietic development. Chromosomal disruptions of the
human CBFA gene are associated with a large percentage of human leukemias. Results:
Utilizing nuclear magnetic resonance spectroscopy we have determined the three-
dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s …
Abstract
Background: CBFA is the DNA-binding subunit of the transcription factor complex called core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality and a profound block in hematopoietic development. Chromosomal disruptions of the human CBFA gene are associated with a large percentage of human leukemias.
Results: Utilizing nuclear magnetic resonance spectroscopy we have determined the three-dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s-type immunoglobulin (Ig) fold. DNA binding by the Runt domain is shown to be mediated by loop regions located at both ends of the Runt domain Ig fold. A putative site for CBFB binding has been identified; the spatial location of this site provides a rationale for the ability of CBFB to modulate the affinity of the Runt domain for DNA.
Conclusions: Structural comparisons demonstrate that the s-type Ig fold found in the Runt domain is conserved in the Ig folds found in the DNA-binding domains of NF-κB, NFAT, p53, STAT-1, and the T-domain. Thus, these proteins form a family of structurally and functionally related DNA-binding domains. Unlike the other members of this family, the Runt domain utilizes loops at both ends of the Ig fold for DNA recognition.
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