3TOA

Human MOF crystal structure with active site lysine partially acetylated

3TOA の概要

• エントリーDOI: 10.2210/pdb3toa/pdb
• 関連するPDBエントリー: 3TO6 3TO7 3TO9 3TOB
• 分子名称: histone acetyltransferase MYST1, ZINC ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: myst protein, hat domain, zinc finger, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9H7Z6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36036.57

構造登録者

Yuan, H.,Ding, E.C.,Marmorstein, R. (登録日: 2011-09-04, 公開日: 2011-11-09, 最終更新日: 2024-10-30)

主引用文献

Yuan, H.,Rossetto, D.,Mellert, H.,Dang, W.,Srinivasan, M.,Johnson, J.,Hodawadekar, S.,Ding, E.C.,Speicher, K.,Abshiru, N.,Perry, R.,Wu, J.,Yang, C.,Zheng, Y.G.,Speicher, D.W.,Thibault, P.,Verreault, A.,Johnson, F.B.,Berger, S.L.,Sternglanz, R.,McMahon, S.B.,Cote, J.,Marmorstein, R.
MYST protein acetyltransferase activity requires active site lysine autoacetylation.
Embo J., 31:58-70, 2011

PubMed Abstract: The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases.

PubMed: 22020126
DOI: 10.1038/emboj.2011.382

実験手法

X-RAY DIFFRACTION (3.004 Å)