6W38

Crystal structure of the FAM46C/Plk4 complex

6W38 の概要

• エントリーDOI: 10.2210/pdb6w38/pdb
• 分子名称: Terminal nucleotidyltransferase 5C, Serine/threonine-protein kinase PLK4 (2 entities in total)
• 機能のキーワード: rna polymerase, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65905.41

構造登録者

Chen, H.,Lu, D.F.,Shang, G.J.,Zhang, X.W. (登録日: 2020-03-09, 公開日: 2020-05-06, 最終更新日: 2023-10-18)

主引用文献

Chen, H.,Lu, D.,Shang, G.,Gao, G.,Zhang, X.
Structural and Functional Analyses of the FAM46C/Plk4 Complex.
Structure, 28:910-921.e4, 2020

PubMed Abstract: FAM46C, a non-canonical poly(A) polymerase, is frequently mutated in multiple myeloma. Loss of function of FAM46C promotes cell survival of multiple myeloma, suggesting a tumor-suppressive role. FAM46C is also essential for fastening sperm head and flagellum, indispensable for male fertility. The molecular mechanisms of these functions of FAM46C remain elusive. We report the crystal structure of FAM46C to provide the basis for its poly(A) polymerase activity and rationalize mutations associated with multiple myeloma. In addition, we found that FAM46C interacts directly with the serine/threonine kinase Plk4, the master regulator of centrosome duplication. We present the structure of FAM46C in complex with the Cryptic Polo-Box 1-2 domains of Plk4. Our structure-based mutational analyses show that the interaction with Plk4 recruits FAM46C to centrosomes. Our data suggest that Plk4-mediated localization of FAM46C enables its regulation of centrosome structure and functions, which may underlie the roles for FAM46C in cell proliferation and sperm development.

PubMed: 32433990
DOI: 10.1016/j.str.2020.04.023

実験手法

X-RAY DIFFRACTION (4.48 Å)