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

FEBS Lett. 2014 Aug 25;588(17):2911-20. doi: 10.1016/j.febslet.2014.07.019. Epub 2014 Jul 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Mice
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism*

Substances

  • ECT2 protein, human
  • GTPase-Activating Proteins
  • Proto-Oncogene Proteins
  • Phosphoserine