Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain.
The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor (CBF) is a heterodimeric enhancer binding protein that is associated with genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP2/CBF are implicated in the cause of the acute human leukemias and in a disorder of bone development known as cleidocranial dysplasia. The common denominator in the natural and mutant forms of this protein is a highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the surface of the RD in contact with the beta subunit, suggesting a mechanism for the enhancement of RD DNA binding by beta. Analysis of leukemogenic mutants within the RD provides molecular insights into the role of this factor in leukemogenesis and cleidocranial dysplasia.
Laboratories of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA.
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T
Nagata
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Gupta
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D
Sorce
W Y
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Kim
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Sali
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Chait
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Shigesada
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Ito
M H
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Werner
D002973:Cleidocranial Dysplasia / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D007938:Leukemia / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000737:chemistry*
D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004247:DNA