Crystal structure of triple-BRCT-domain of ECT2 and insights into the binding characteristics to CYK-4

Abstract

Homo sapiens ECT2 is a cell cycle regulator that plays critical roles in cytokinesis. ECT2 activity is restrained during interphase via intra-molecular interactions that involve its N-terminal triple-BRCT-domain and its C-terminal DH-PH domain. At anaphase, this self-inhibitory mechanism is relieved by Plk1-phosphorylated CYK-4, which directly engages the ECT2 BRCT domain. To provide a structural perspective for this auto-inhibitory property, we solved the crystal structure of the ECT2 triple-BRCT-domain. In addition, we systematically analyzed the interaction between the ECT2 BRCT domains with phospho-peptides derived from its binding partner CYK-4, and have identified Ser164 as the major phospho-residue that links CYK-4 to the second ECT2 BRCT domain.

Keywords: Auto-inhibition; Binding pocket; Phospho-peptide; The epithelial cell transforming protein 2; Triple-BRCT-domain.