5DNJ

Mouse Polo-box domain and Peptide analog 702

5DNJ の概要

• エントリーDOI: 10.2210/pdb5dnj/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002222
• 分子名称: Serine/threonine-protein kinase PLK1, peptide 707-56A-SER-TPO-NH2 (3 entities in total)
• 機能のキーワード: plk1, emi2, protein kinase, meiosis, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Nucleus : Q07832
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28136.72

構造登録者

Namgoong, S.,Han, Y.H. (登録日: 2015-09-10, 公開日: 2016-02-24, 最終更新日: 2024-10-09)

主引用文献

Jia, J.L.,Han, Y.H.,Kim, H.C.,Ahn, M.,Kwon, J.W.,Luo, Y.,Gunasekaran, P.,Lee, S.J.,Lee, K.S.,Bang, J.K.,Kim, N.H.,Namgoong, S.
Structural basis for recognition of Emi2 by Polo-like kinase 1 and development of peptidomimetics blocking oocyte maturation and fertilization.
Sci Rep, 5:14626-14626, 2015

PubMed Abstract: In a mammalian oocyte, completion of meiosis is suspended until fertilization by a sperm, and the cell cycle is arrested by a biochemical activity called cytostatic factor (CSF). Emi2 is one of the CSFs, and it maintains the protein level of maturation promoting factor (MPF) by inhibiting ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Degradation of Emi2 via ubiquitin-mediated proteolysis after fertilization requires phosphorylation by Polo-like kinase 1 (Plk1). Therefore, recognition and phosphorylation of Emi2 by Plk1 are crucial steps for cell cycle resumption, but the binding mode of Emi2 and Plk1 is poorly understood. Using biochemical assays and X-ray crystallography, we found that two phosphorylated threonines (Thr(152) and Thr(176)) in Emi2 are each responsible for the recruitment of one Plk1 molecule by binding to its C-terminal polo box domain (PBD). We also found that meiotic maturation and meiosis resumption via parthenogenetic activation were impaired when Emi2 interaction with Plk1-PBD was blocked by a peptidomimetic called 103-8. Because of the inherent promiscuity of kinase inhibitors, our results suggest that targeting PBD of Plk1 may be an effective strategy for the development of novel and specific contraceptive agents that block oocyte maturation and/or fertilization.

PubMed: 26459104
DOI: 10.1038/srep14626

実験手法

X-RAY DIFFRACTION (2.3 Å)