2wbu | pdb_00002wbu
CRYSTAL STRUCTURE OF THE ZINC FINGER DOMAIN OF KLF4 BOUND TO ITS TARGET DNA
Structural highlights
FunctionKLF4_MOUSE Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription (By similarity).[1] [2] [3] [4] [5] [6] [7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedKrueppel-like factor 4 (Klf4) belongs to the Sp/Klf family of zinc-finger transcription factors and is indispensable for terminal maturation of epithelial tissues. Furthermore, it is part of a small set of proteins that are used to generate pluripotent embryonic stem cells from differentiated tissues. Herein, we describe that a Klf4 zinc-finger domain mutant induces self-renewal and block of maturation, while wild-type Klf4 induces terminal macrophage differentiation. Moreover, we present the crystal structure of the zinc-finger domain of Klf4 bound to its target DNA, revealing that primarily the two C-terminal zinc-finger motifs are required for site specificity. Lack of those two zinc fingers leads to deficiency of Klf4 to induce macrophage differentiation. The first zinc finger, on the other hand, inhibits the otherwise cryptic self-renewal and block of differentiation activity of Klf4. Our data show that impairing the DNA binding could potentially contribute to a monocytic leukemia. The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation.,Schuetz A, Nana D, Rose C, Zocher G, Milanovic M, Koenigsmann J, Blasig R, Heinemann U, Carstanjen D Cell Mol Life Sci. 2011 Sep;68(18):3121-31. Epub 2011 Feb 3. PMID:21290164[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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