4COS

Crystal structure of the PHD-Bromo-PWWP cassette of human PRKCBP1

4COS の概要

• エントリーDOI: 10.2210/pdb4cos/pdb
• 分子名称: PROTEIN KINASE C-BINDING PROTEIN 1, ZINC ION, 1,4-DIETHYLENE DIOXIDE, ... (4 entities in total)
• 機能のキーワード: transcription, phd domain, bromo domain, pwwp domain
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus : Q9ULU4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38206.17

構造登録者

Krojer, T.,Savitsky, P.,Newman, J.A.,Cooper, C.D.O.,von Delft, F.,Arrowsmith, C.H.,Bountra, C.,Edwards, A.,Filippakopoulos, P. (登録日: 2014-01-30, 公開日: 2014-03-05, 最終更新日: 2024-05-08)

主引用文献

Savitsky, P.,Krojer, T.,Fujisawa, T.,Lambert, J.P.,Picaud, S.,Wang, C.Y.,Shanle, E.K.,Krajewski, K.,Friedrichsen, H.,Kanapin, A.,Goding, C.,Schapira, M.,Samsonova, A.,Strahl, B.D.,Gingras, A.C.,Filippakopoulos, P.
Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin.
Cell Rep, 17:2724-2737, 2016

PubMed Abstract: Elucidation of interactions involving DNA and histone post-translational-modifications (PTMs) is essential for providing insights into complex biological functions. Reader assemblies connected by flexible linkages facilitate avidity and increase affinity; however, little is known about the contribution to the recognition process of multiple PTMs because of rigidity in the absence of conformational flexibility. Here, we resolve the crystal structure of the triple reader module (PHD-BRD-PWWP) of ZMYND8, which forms a stable unit capable of simultaneously recognizing multiple histone PTMs while presenting a charged platform for association with DNA. Single domain disruptions destroy the functional network of interactions initiated by ZMYND8, impairing recruitment to sites of DNA damage. Our data establish a proof of principle that rigidity can be compensated by concomitant DNA and histone PTM interactions, maintaining multivalent engagement of transient chromatin states. Thus, our findings demonstrate an important role for rigid multivalent reader modules in nucleosome binding and chromatin function.

PubMed: 27926874
DOI: 10.1016/j.celrep.2016.11.014

実験手法

X-RAY DIFFRACTION (1.67 Å)