4N7Z

Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep192 N-terminal fragment

4N7Z の概要

• エントリーDOI: 10.2210/pdb4n7z/pdb
• 関連するPDBエントリー: 4N7V
• 分子名称: Serine/threonine-protein kinase PLK4, Centrosomal protein of 192 kDa (3 entities in total)
• 機能のキーワード: k/r crater, d-rich motif, centriole biogenesis, cep192, centrosome, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole: O00444
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33242.58

構造登録者

Park, S.-Y.,Park, J.-E.,Tian, L.,Kim, T.-S.,Yang, W.,Lee, K.S. (登録日: 2013-10-16, 公開日: 2014-07-02, 最終更新日: 2023-09-20)

主引用文献

Park, S.Y.,Park, J.E.,Kim, T.S.,Kim, J.H.,Kwak, M.J.,Ku, B.,Tian, L.,Murugan, R.N.,Ahn, M.,Komiya, S.,Hojo, H.,Kim, N.H.,Kim, B.Y.,Bang, J.K.,Erikson, R.L.,Lee, K.W.,Kim, S.J.,Oh, B.H.,Yang, W.,Lee, K.S.
Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis.
Nat.Struct.Mol.Biol., 21:696-703, 2014

PubMed Abstract: Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. We show that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal-structure analyses revealed that Cep192- and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner. The Cep152 peptide bound to the CPB markedly better than did the Cep192 peptide and effectively 'snatched' the CPB away from a preformed CPB-Cep192 peptide complex. A cancer-associated Cep152 mutation impairing the Plk4 interaction induced defects in procentriole assembly and chromosome segregation. Thus, Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer.

PubMed: 24997597
DOI: 10.1038/nsmb.2846

実験手法

X-RAY DIFFRACTION (2.85 Å)