5WP3

Crystal Structure of EED in complex with EB22

5WP3 の概要

• エントリーDOI: 10.2210/pdb5wp3/pdb
• 分子名称: Polycomb protein EED, EB22, UNKNOWN ATOM OR ION (3 entities in total)
• 機能のキーワード: structural genomics, structural genomics consortium, sgc, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: O75530
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56436.58

構造登録者

Dong, C.,Tempel, W.,Zhu, L.,Moody, J.D.,Baker, D.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (登録日: 2017-08-03, 公開日: 2017-09-13, 最終更新日: 2024-10-16)

主引用文献

Moody, J.D.,Levy, S.,Mathieu, J.,Xing, Y.,Kim, W.,Dong, C.,Tempel, W.,Robitaille, A.M.,Dang, L.T.,Ferreccio, A.,Detraux, D.,Sidhu, S.,Zhu, L.,Carter, L.,Xu, C.,Valensisi, C.,Wang, Y.,Hawkins, R.D.,Min, J.,Moon, R.T.,Orkin, S.H.,Baker, D.,Ruohola-Baker, H.
First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.
Proc. Natl. Acad. Sci. U.S.A., 114:10125-10130, 2017

PubMed Abstract: The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with subnanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESCs) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development.

PubMed: 28864533
DOI: 10.1073/pnas.1706907114

実験手法

X-RAY DIFFRACTION (2.55 Å)