5EUP

Structure of the Drosophila melanogaster CP190 BTB domain

5EUP の概要

• エントリーDOI: 10.2210/pdb5eup/pdb
• 分子名称: Centrosome-associated zinc finger protein CP190 (2 entities in total)
• 機能のキーワード: btb domain cp190 chromatin insulator centrosome, structural protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16176.71

構造登録者

Plevock, K.M.,Galletta, B.J.,Slep, K.C.,Rusan, N.M. (登録日: 2015-11-19, 公開日: 2015-12-23, 最終更新日: 2024-03-06)

主引用文献

Plevock, K.M.,Galletta, B.J.,Slep, K.C.,Rusan, N.M.
Newly Characterized Region of CP190 Associates with Microtubules and Mediates Proper Spindle Morphology in Drosophila Stem Cells.
Plos One, 10:e0144174-e0144174, 2015

PubMed Abstract: CP190 is a large, multi-domain protein, first identified as a centrosome protein with oscillatory localization over the course of the cell cycle. During interphase it has a well-established role within the nucleus as a chromatin insulator. Upon nuclear envelope breakdown, there is a striking redistribution of CP190 to centrosomes and the mitotic spindle, in addition to the population at chromosomes. Here, we investigate CP190 in detail by performing domain analysis in cultured Drosophila S2 cells combined with protein structure determination by X-ray crystallography, in vitro biochemical characterization, and in vivo fixed and live imaging of cp190 mutant flies. Our analysis of CP190 identifies a novel N-terminal centrosome and microtubule (MT) targeting region, sufficient for spindle localization. This region consists of a highly conserved BTB domain and a linker region that serves as the MT binding domain. We present the 2.5 Å resolution structure of the CP190 N-terminal 126 amino acids, which adopts a canonical BTB domain fold and exists as a stable dimer in solution. The ability of the linker region to robustly localize to MTs requires BTB domain-mediated dimerization. Deletion of the linker region using CRISPR significantly alters spindle morphology and leads to DNA segregation errors in the developing Drosophila brain neuroblasts. Collectively, we highlight a multivalent MT-binding architecture in CP190, which confers distinct subcellular cytoskeletal localization and function during mitosis.

PubMed: 26649574
DOI: 10.1371/journal.pone.0144174

実験手法

X-RAY DIFFRACTION (2.5 Å)