4hc9 | pdb_00004hc9
DNA binding by GATA transcription factor-complex 3
Structural highlights
Disease[GATA3_HUMAN] Precursor B-cell acute lymphoblastic leukemia;Hypoparathyroidism - deafness - renal disease. The disease is caused by mutations affecting the gene represented in this entry. Function[GATA3_HUMAN] Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses.[1] Publication Abstract from PubMedGATA transcription factors regulate transcription during development and differentiation by recognizing distinct GATA sites with a tandem of two conserved zinc fingers, and by mediating long-range DNA looping. However, the molecular basis of these processes is not well understood. Here, we determined three crystal structures of the full DNA-binding domain (DBD) of human GATA3 protein, which contains both zinc fingers, in complex with different DNA sites. In one structure, both zinc fingers wrap around a palindromic GATA site, cooperatively enhancing the binding affinity and kinetic stability. Strikingly, in the other two structures, the two fingers of GATA DBD bind GATA sites on different DNA molecules, thereby bridging two separate DNA fragments. This was confirmed in solution by an in-gel fluorescence resonance energy transfer analysis. These findings not only provide insights into the structure and function of GATA proteins but also shed light on the molecular basis of long-range gene regulation. DNA Binding by GATA Transcription Factor Suggests Mechanisms of DNA Looping and Long-Range Gene Regulation.,Chen Y, Bates DL, Dey R, Chen PH, Machado AC, Laird-Offringa IA, Rohs R, Chen L Cell Rep. 2012 Nov 29;2(5):1197-206. doi: 10.1016/j.celrep.2012.10.012. Epub 2012, Nov 8. PMID:23142663[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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