Mutations in DNA-binding loop of NFAT5 transcription factor produce unique outcomes on protein-DNA binding and dynamics.

ABSTRACT: The nuclear factor of activated T cells 5 (NFAT5 or TonEBP) is a Rel family transcriptional activator and is activated by hypertonic conditions. Several studies point to a possible connection between nuclear translocation and DNA binding; however, the mechanism of NFAT5 nuclear translocation and the effect of DNA binding on retaining NFAT5 in the nucleus are largely unknown. Recent experiments showed that different mutations introduced in the DNA-binding loop and dimerization interface were important for DNA binding and some of them decreased the nuclear-cytoplasm ratio of NFAT5. To understand the mechanisms of these mutations, we model their effect on protein dynamics and DNA binding. We show that the NFAT5 complex without DNA is much more flexible than the complex with DNA. Moreover, DNA

SUBMITTER: Li M 

PROVIDER: S-EPMC3807822 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature