Structural Insight into the Zinc Finger CW Domain as a Histone Modification Reader

SummaryThe zinc finger CW (zf-CW) domain is a motif of about 60 residues that is frequently found in proteins involved in epigenetic regulation. Here, we determined the NMR solution structure of the zf-CW domain of the human zf-CW and PWWP domain containing protein 1 (ZCWPW1). The zf-CW domain adopts a new fold in which a zinc ion is coordinated tetrahedrally by four conserved Cys ligand residues. The tertiary structure of the zf-CW domain partially resembles that adopted by the plant homeo domain (PHD) finger bound to the histone tail, suggesting that the zf-CW domain and the PHD finger have similar functions. The solution structure of the complex of the zf-CW domain with the histone H3 tail peptide (1-10) with trimethylated K4 clarified its binding mode. Our structural and biochemical studies have identified the zf-CW domain as a member of the histone modification reader modules for epigenetic regulation.

► This is the first solution structure for zf-CW domain as a novel zinc finger
► Preference and binding affinities between zf-CW and H3K4me have been determined
► The first complex structure of zf-CW-H3K4me3 showed a novel binding mode
► The zf-CW domain was identified as a new member of the histone modification reader.