4CY5

Crystal structure of the NSL1-WDS-NSL2 complex.

4CY5 の概要

• エントリーDOI: 10.2210/pdb4cy5/pdb
• 関連するPDBエントリー: 4CY1 4CY2 4CY3
• 分子名称: PROTEIN WILL DIE SLOWLY, DIM GAMMA-TUBULIN 1, CG4699, ISOFORM D, ... (4 entities in total)
• 機能のキーワード: transcription, epigenetic regulator, histone acetylation, chromatin
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 38002.91

構造登録者

Dias, J.,Brettschneider, J.,Cusack, S.,Kadlec, J. (登録日: 2014-04-10, 公開日: 2014-05-14, 最終更新日: 2023-12-20)

主引用文献

Dias, J.,Van Nguyen, N.,Georgiev, P.,Gaub, A.,Brettschneider, J.,Cusack, S.,Kadlec, J.,Akhtar, A.
Structural Analysis of the Kansl1/Wdr5/Kansl2 Complex Reveals that Wdr5 is Required for Efficient Assembly and Chromatin Targeting of the Nsl Complex.
Genes Dev., 28:929-, 2014

PubMed Abstract: The subunits of the nonspecific lethal (NSL) complex, which include the histone acetyltransferase MOF (males absent on the first), play important roles in various cellular functions, including transcription regulation and stem cell identity maintenance and reprogramming, and are frequently misregulated in disease. Here, we provide the first biochemical and structural insights into the molecular architecture of this large multiprotein assembly. We identified several direct interactions within the complex and show that KANSL1 acts as a scaffold protein interacting with four other subunits, including WDR5, which in turn binds KANSL2. Structural analysis of the KANSL1/WDR5/KANSL2 subcomplex reveals how WDR5 is recruited into the NSL complex via conserved linear motifs of KANSL1 and KANSL2. Using structure-based KANSL1 mutants in transgenic flies, we show that the KANSL1-WDR5 interaction is required for proper assembly, efficient recruitment of the NSL complex to target promoters, and fly viability. Our data clearly show that the interactions of WDR5 with the MOF-containing NSL complex and MLL/COMPASS histone methyltransferase complexes are mutually exclusive. We propose that rather than being a shared subunit, WDR5 plays an important role in assembling distinct histone-modifying complexes with different epigenetic regulatory roles.

PubMed: 24788516
DOI: 10.1101/GAD.240200.114

実験手法

X-RAY DIFFRACTION (2.3 Å)