The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains.
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-kappaB, 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.
Berardi
M J
MJ
Department of Molecular Physiology and Biological Physics University of Virginia, Charlottesville, VA 22906, USA.
Sun
C
C
Zehr
M
M
Abildgaard
F
F
Peng
J
J
Speck
N A
NA
Bushweller
J H
JH
D000818:Animals; D001665:Binding Sites; D050676:Core Binding Factor Alpha 2 Subunit; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D015800:Protozoan Proteins; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D011518:Proto-Oncogene Proteins; D015800:Protozoan Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors; C400205:cbfA protein, Dictyostelium discoideum; D004247:DNA