6E2H

Crystal structure of human Ash2L (SPRY domain and SDI motif) in complex with full length DPY-30

6E2H の概要

• エントリーDOI: 10.2210/pdb6e2h/pdb
• 分子名称: Set1/Ash2 histone methyltransferase complex subunit ASH2, Protein dpy-30 homolog (3 entities in total)
• 機能のキーワード: histone, epigenetics, set1, mll, lysine methylation, nucleosome, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 46611.62

構造登録者

Joshi, M.,Brunzelle, J.S.,Couture, J.F. (登録日: 2018-07-11, 公開日: 2018-08-08, 最終更新日: 2023-10-11)

主引用文献

Haddad, J.F.,Yang, Y.,Takahashi, Y.H.,Joshi, M.,Chaudhary, N.,Woodfin, A.R.,Benyoucef, A.,Yeung, S.,Brunzelle, J.S.,Skiniotis, G.,Brand, M.,Shilatifard, A.,Couture, J.F.
Structural Analysis of the Ash2L/Dpy-30 Complex Reveals a Heterogeneity in H3K4 Methylation.
Structure, 26:1594-, 2018

PubMed Abstract: Dpy-30 is a regulatory subunit controlling the histone methyltransferase activity of the KMT2 enzymes in vivo. Paradoxically, in vitro methyltransferase assays revealed that Dpy-30 only modestly participates in the positive heterotypic allosteric regulation of these methyltransferases. Detailed genome-wide, molecular and structural studies reveal that an extensive network of interactions taking place at the interface between Dpy-30 and Ash2L are critical for the correct placement, genome-wide, of H3K4me2 and H3K4me3 but marginally contribute to the methyltransferase activity of KMT2 enzymes in vitro. Moreover, we show that H3K4me2 peaks persisting following the loss of Dpy-30 are found in regions of highly transcribed genes, highlighting an interplay between Complex of Proteins Associated with SET1 (COMPASS) kinetics and the cycling of RNA polymerase to control H3K4 methylation. Overall, our data suggest that Dpy-30 couples its modest positive heterotypic allosteric regulation of KMT2 methyltransferase activity with its ability to help the positioning of SET1/COMPASS to control epigenetic signaling.

PubMed: 30270175
DOI: 10.1016/j.str.2018.08.004

実験手法

X-RAY DIFFRACTION (2.236 Å)