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.
Yang Zou  1 ,  Zhenhua Shao  1 ,  Junhui Peng  1 ,  Fudong Li  1 ,  Deshun Gong  1 ,  Chongyuan Wang  1 ,  Xiaobing Zuo  2 ,  Zhiyong Zhang  1 ,  Jihui Wu  1 ,  Yunyu Shi  1 ,  Qingguo Gong  3
Affiliations
  • 1. Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  • 2. X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60349, USA.
  • 3. Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: [email protected].
PMID: 25068414 DOI: 10.1016/j.febslet.2014.07.019
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.