6TL1

Crystal structure of the TASOR pseudo-PARP domain

6TL1 の概要

• エントリーDOI: 10.2210/pdb6tl1/pdb
• 分子名称: Protein TASOR, GLYCEROL (3 entities in total)
• 機能のキーワード: nuclear protein; transcriptional repressor; epigenetic silencing; histone h3 lysine 9 methylation (h3k9me3); transposable element; line1 element; rna-binding protein, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49736.95

構造登録者

Douse, C.H.,Timms, R.T.,Freund, S.M.V.,Modis, Y. (登録日: 2019-11-29, 公開日: 2020-09-16, 最終更新日: 2024-05-15)

主引用文献

Douse, C.H.,Tchasovnikarova, I.A.,Timms, R.T.,Protasio, A.V.,Seczynska, M.,Prigozhin, D.M.,Albecka, A.,Wagstaff, J.,Williamson, J.C.,Freund, S.M.V.,Lehner, P.J.,Modis, Y.
TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control.
Nat Commun, 11:4940-4940, 2020

PubMed Abstract: The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits - TASOR, MPP8 and Periphilin - contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets.

PubMed: 33009411
DOI: 10.1038/s41467-020-18761-6

実験手法

X-RAY DIFFRACTION (2.03 Å)