Cysteine 397 plays important roles in the folding of the neuron-restricted silencer factor/RE1-silencing transcription factor.

The neuron-restrictive silencer factor/RE1-silencing transcription factor (NRSF/REST) is regarded as not only a key transcriptional repressor but also an activator in neuron gene expression by specifically interacting with neuron-restrictive silencer element (NRSE/RE1) dsDNA and small NRSE/RE1 dsRNA, respectively. But its exact mechanism remains unclear. One major problem is that it is hard to obtain its functional multiple zinc finger (ZnF) domains in a large quantity for further structural studies. To address this issue, in this study, we for the first time attained soluble NRSF/REST functional domains named as ZnF5-8, ZnF4-8, ZnF3-8 and ZnF2-8 containing four, five, six and seven ZnF motifs in tandem, respectively, by using Circular Dichroism (CD) spectrum and two-dimensional (2D) nucleic magnetic resonance (NMR) (1)H-(1)H NOESY spectrum to monitor the folding of each single ZnF peptide. The data indicated that the residue cysteine 397 (Cys397) plays important roles in the global folding of NRSF/REST multiple ZnFs domain.