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Structural Basis of Emi2 Recognition by Polo-Box Domain of Polo-like Kinase 1 and Effects of Structure-Derived Antagonist in Oocyte Maturation and Fertillization

초록

영어

In meiosis, Emi2 plays important role as CSF (Cytostatic Factor) to make the oocyte arrested in mII stage by the inhibition of APC/C (anaphase promoting complex/cyclosome). Once the oocyte fertilized, Emi2 was destabilized and degraded. For the degradation of Emi2, calcium signaling activate calmodulin-dependent protein kinase (CaMK) and phosphorylate emi2. Phosphorylated emi2 is recognized by polo-box domain of polo-like kinase 1 (Plk1) and further degradated by ubiquitin-dependent proteolysis. But recognition of Plk1 and emi2 is unknown. In this works, we determined the high-resolution crystal structure of polo-box domain of Plk1 and phosphorylated emi2 peptide at 1.90Å. Determined structure revealed that several unique features, including binding of Phe169 in the tyrosin-rich hydrophobic pocket. This is the first report of crystallization that Plk1-emi2 complex. Based on the complex structure, we designed the peptide analogs which pontentially inhibits recognition of Emi2 by Plk1 and assessed its biological activity in oocyte maturation and pathernogenetic activation. Injection of AB103-8, the inhibitor of Plk1 Polo-box domain, in mouse oocytes, induced the maturation arrest in GV stage and the delay in mII parthenogenetic activation. Further investigations of the mechanism that Plk1 involved into the Emi2 mII arrest are underway.

저자정보

  • Jia-Jia Lin Department of Animal Sciences, Chungbuk National University
  • Young-Hyun Han Department of Animal Sciences, Chungbuk National University
  • Jung-Woo Kwon Department of Animal Sciences, Chungbuk National University
  • Yong-Nan Xu Department of Animal Sciences, Chungbuk National University
  • Yi-Bo Luo Department of Animal Sciences, Chungbuk National University
  • Yu-Jin Jo Department of Animal Sciences, Chungbuk National University
  • Chang-Eun Park Departmet of Biomedical Laboratory Science, Namseoul University
  • Jung-Kyu Baang Korean Basic Science Institute
  • Suk Namgoong Department of Animal Sciences, Chungbuk National University
  • Nam-Hyung Kim Department of Animal Sciences, Chungbuk National University

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