1co1

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FOLD OF THE CBFA

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Leukemia, acute myeloid OMIM:[151385], Platelet disorder, familial, with associated myeloid malignancy OMIM:[151385], Rheumatoid arthritis, susceptibility to OMIM:[151385]

About this Structure

1CO1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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., Berardi MJ, Sun C, Zehr M, Abildgaard F, Peng J, Speck NA, Bushweller JH, Structure. 1999 Oct 15;7(10):1247-56. PMID:10545320

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