5ERC

X-ray crystal structure of BRPF1 PZP domain

5ERC の概要

• エントリーDOI: 10.2210/pdb5erc/pdb
• 分子名称: Peregrin, ZINC ION, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: reader domain, methyllysine, dna, h3 histone, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20035.84

構造登録者

Klein, B.J.,Andrews, F.H.,Kutateladze, T.G. (登録日: 2015-11-13, 公開日: 2015-12-30, 最終更新日: 2024-03-06)

主引用文献

Klein, B.J.,Muthurajan, U.M.,Lalonde, M.E.,Gibson, M.D.,Andrews, F.H.,Hepler, M.,Machida, S.,Yan, K.,Kurumizaka, H.,Poirier, M.G.,Cote, J.,Luger, K.,Kutateladze, T.G.
Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation.
Nucleic Acids Res., 44:472-484, 2016

PubMed Abstract: BRPF1 (bromodomain PHD finger 1) is a core subunit of the MOZ histone acetyltransferase (HAT) complex, critical for normal developmental programs and implicated in acute leukemias. BRPF1 contains a unique assembly of zinc fingers, termed a PZP domain, the physiological role of which remains unclear. Here, we elucidate the structure-function relationship of this novel epigenetic reader and detail the biological and mechanistic consequences of its interaction with nucleosomes. PZP has a globular architecture and forms a 2:1 stoichiometry complex with the nucleosome, bivalently interacting with histone H3 and DNA. This binding impacts the nucleosome dynamics, shifting the DNA unwrapping/rewrapping equilibrium toward the unwrapped state and increasing DNA accessibility. We demonstrate that the DNA-binding function of the BRPF1 PZP domain is required for the MOZ-BRPF1-ING5-hEaf6 HAT complex to be recruited to chromatin and to acetylate nucleosomal histones. Our findings reveal a novel link between chromatin dynamics and MOZ-mediated acetylation.

PubMed: 26626149
DOI: 10.1093/nar/gkv1321

実験手法

X-RAY DIFFRACTION (2.05 Å)