Core NFATC1 in complex with DNA

Transcription factors belonging to the NFAT (nuclear factor of the activated T cell) family have been found to control the activation of genes which encode for cytokines as well as their receptors. NFAT is normally found in the cytoplasm of resting T cells. However, it translocates to the nucleus when it becomes dephosphorylated by a Ca2+-activated Serine/Threonine phosphatase, calcineurin. NFAT activates gene transcription cooperatively along with another transcription factor, AP-1, which is induced by a p21ras-dependent signaling pathway.
Proteins of the NFAT family possess two regions of homology; the N-terminal domain controls the Ca2+-dependent subcellular location whereas the C-terminal domain binds DNA sequence-specifically along with AP-1. NFATC1 is the DNA-binding domain (NFATC1-DBD) of NFATC1 C-terminal domain. The DNA recognition domain of the NFATC1 forms a binary complex with a 12-base pair oligonucleotide DNA duplex which contains the ARRE2 sequence.


Core NFATC1, DNA-Binding Domain

NFATC1-DBD is a 178 amino acid residue long polypeptide. However, NFATC1-DBD is actually residues 416-591 in the entire human transcription factor NFATC. NFATC1-DBD exhibits a common fold with the DNA-binding domain of Rel family proteins. It forms a 10-stranded beta-barrel which is similar to the s-type domains of the immunoglobin (Ig) superfamily. All beta sheets are shown in purple. It also contains a small right-handed alpha-helix which is shown in red.


DNA, 12 bp oligonucleotide

This 12-bp long oligonucleotide of DNA (deoxyribonucleic acid) contains the core NFAT recognition site from murine ARRE2. In complex with NFATC1, the DNA is unbent and is typical of a B-form duplex. A small minor groove compression occurs however at positions 4-6. The nucleotide sequence of the DNA is as follows: 5'-CGAGGAAAATTG-3'.


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