Structural highlights
Function
[NFAC2_HUMAN] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.[1]
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 PubMed
The host factor, nuclear factor of activated T-cells (NFAT), regulates the transcription and replication of HIV-1. Here, we have determined the crystal structure of the DNA binding domain of NFAT bound to the HIV-1 long terminal repeat (LTR) tandem kappaB enhancer element at 3.05 A resolution. NFAT binds as a dimer to the upstream kappaB site (Core II), but as a monomer to the 3' end of the downstream kappaB site (Core I). The DNA shows a significant bend near the 5' end of Core I, where a lysine residue from NFAT bound to the 3' end of Core II inserts into the minor groove and seems to cause DNA bases to flip out. Consistent with this structural feature, the 5' end of Core I become hypersensitive to dimethylsulfate in the in vivo footprinting upon transcriptional activation of the HIV-1 LTR. Our studies provide a basis for further investigating the functional mechanisms of NFAT in HIV-1 transcription and replication.
Crystal structure of NFAT bound to the HIV-1 LTR tandem kappaB enhancer element.,Bates DL, Barthel KK, Wu Y, Kalhor R, Stroud JC, Giffin MJ, Chen L Structure. 2008 May;16(5):684-94. PMID:18462673[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yiu GK, Kaunisto A, Chin YR, Toker A. NFAT promotes carcinoma invasive migration through glypican-6. Biochem J. 2011 Nov 15;440(1):157-66. doi: 10.1042/BJ20110530. PMID:21871017 doi:10.1042/BJ20110530
- ↑ Bates DL, Barthel KK, Wu Y, Kalhor R, Stroud JC, Giffin MJ, Chen L. Crystal structure of NFAT bound to the HIV-1 LTR tandem kappaB enhancer element. Structure. 2008 May;16(5):684-94. PMID:18462673 doi:10.1016/j.str.2008.01.020
