8QR1

Cryo-EM structure of the human Tip60 complex

これはPDB形式変換不可エントリーです。

8QR1 の概要

• エントリーDOI: 10.2210/pdb8qr1/pdb
• EMDBエントリー: 18611
• 分子名称: E1A-binding protein p400, Enhancer of polycomb homolog 1, DNA methyltransferase 1-associated protein 1, ... (8 entities in total)
• 機能のキーワード: eukaryotic transcription, histone acetyltransferase, chromatin remodeling, complex, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 966838.81

構造登録者

Li, C.,Smirnova, E.,Schnitzler, C.,Crucifix, C.,Concordet, J.P.,Brion, A.,Poterszman, A.,Schultz, P.,Papai, G.,Ben-Shem, A. (登録日: 2023-10-06, 公開日: 2024-08-07, 最終更新日: 2024-12-04)

主引用文献

Li, C.,Smirnova, E.,Schnitzler, C.,Crucifix, C.,Concordet, J.P.,Brion, A.,Poterszman, A.,Schultz, P.,Papai, G.,Ben-Shem, A.
Structure of the human TIP60-C histone exchange and acetyltransferase complex.
Nature, 635:764-769, 2024

PubMed Abstract: Chromatin structure is a key regulator of DNA transcription, replication and repair. In humans, the TIP60-EP400 complex (TIP60-C) is a 20-subunit assembly that affects chromatin structure through two enzymatic activities: ATP-dependent exchange of histone H2A-H2B for H2A.Z-H2B, and histone acetylation. In yeast, however, these activities are performed by two independent complexes-SWR1 and NuA4, respectively. How the activities of the two complexes are merged into one supercomplex in humans, and what this association entails for the structure and mechanism of the proteins and their recruitment to chromatin, are unknown. Here we describe the structure of the endogenous human TIP60-C. We find a three-lobed architecture composed of SWR1-like (SWR1L) and NuA4-like (NuA4L) parts, which associate with a TRRAP activator-binding module. The huge EP400 subunit contains the ATPase motor, traverses the junction between SWR1L and NuA4L twice and constitutes the scaffold of the three-lobed architecture. NuA4L is completely rearranged compared with its yeast counterpart. TRRAP is flexibly tethered to NuA4L-in stark contrast to its robust connection to the completely opposite side of NuA4 in yeast. A modelled nucleosome bound to SWR1L, supported by tests of TIP60-C activity, suggests that some aspects of the histone exchange mechanism diverge from what is seen in yeast. Furthermore, a fixed actin module (as opposed to the mobile actin subcomplex in SWR1; ref. ), the flexibility of TRRAP and the weak effect of extranucleosomal DNA on exchange activity lead to a different, activator-based mode of enlisting TIP60-C to chromatin.

PubMed: 39260417
DOI: 10.1038/s41586-024-08011-w

実験手法

ELECTRON MICROSCOPY (2.4 Å)