9BHD

PRMT1-Octamer

9BHD の概要

• エントリーDOI: 10.2210/pdb9bhd/pdb
• EMDBエントリー: 44541
• 分子名称: Protein arginine N-methyltransferase 1, S-ADENOSYL-L-HOMOCYSTEINE (2 entities in total)
• 機能のキーワード: prmt1 octamer, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 309354.07

構造登録者

Nadendla, E.K.,Wang, C.H. (登録日: 2024-04-19, 公開日: 2025-04-30, 最終更新日: 2026-01-28)

主引用文献

Dang, T.,EswarKumar, N.,Tripathi, S.K.,Yan, C.,Wang, C.H.,Cao, M.,Paul, T.K.,Agboluaje, E.O.,Xiong, M.P.,Ivanov, I.,Ho, M.C.,Zheng, Y.G.
Oligomerization of protein arginine methyltransferase 1 and its functional impact on substrate arginine methylation.
J.Biol.Chem., 300:107947-107947, 2024

PubMed Abstract: Protein arginine methyltransferases (PRMTs) are important posttranslational modifying enzymes in eukaryotic proteins and regulate diverse pathways from gene transcription, RNA splicing, and signal transduction to metabolism. Increasing evidence supports that PRMTs exhibit the capacity to form higher-order oligomeric structures, but the structural basis of PRMT oligomerization and its functional consequence are elusive. Herein, we revealed for the first time different oligomeric structural forms of the predominant arginine methyltransferase PRMT1 using cryo-EM, which included tetramer (dimer of dimers), hexamer (trimer of dimers), octamer (tetramer of dimers), decamer (pentamer of dimers), and also helical filaments. Through a host of biochemical assays, we showed that PRMT1 methyltransferase activity was substantially enhanced as a result of the high-ordered oligomerization. High-ordered oligomerization increased the catalytic turnover and the multimethylation processivity of PRMT1. Presence of a catalytically dead PRMT1 mutant also enhanced the activity of WT PRMT1, pointing out a noncatalytic role of oligomerization. Structural modeling demonstrates that oligomerization enhances substrate retention at the PRMT1 surface through electrostatic force. Our studies offered key insights into PRMT1 oligomerization and established that oligomerization constitutes a novel molecular mechanism that positively regulates the enzymatic activity of PRMTs in biology.

PubMed: 39491649
DOI: 10.1016/j.jbc.2024.107947

実験手法

ELECTRON MICROSCOPY (3.38 Å)