5L6D

Crystal structure of the human METTL3-METTL14 complex bound to SAH

5L6D の概要

• エントリーDOI: 10.2210/pdb5l6d/pdb
• 分子名称: N6-adenosine-methyltransferase 70 kDa subunit, N6-adenosine-methyltransferase subunit METTL14, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• 機能のキーワード: rna methyltransferase n6-adenine methylation rossmann fold, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q86U44 Q9HCE5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59844.46

構造登録者

Sledz, P.,Jinek, M. (登録日: 2016-05-29, 公開日: 2016-10-12)

主引用文献

Sledz, P.,Jinek, M.
Structural insights into the molecular mechanism of the m(6)A writer complex.
Elife, 5:-, 2016

PubMed Abstract: Methylation of adenosines at the N(6) position (m(6)A) is a dynamic and abundant epitranscriptomic mark that regulates critical aspects of eukaryotic RNA metabolism in numerous biological processes. The RNA methyltransferases METTL3 and METTL14 are components of a multisubunit m(6)A writer complex whose enzymatic activity is substantially higher than the activities of METTL3 or METTL14 alone. The molecular mechanism underpinning this synergistic effect is poorly understood. Here we report the crystal structure of the catalytic core of the human m(6)A writer complex comprising METTL3 and METTL14. The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. These studies illuminate the molecular mechanism and evolutionary history of eukaryotic m(6)A modification in post-transcriptional genome regulation.

PubMed: 27627798
DOI: 10.7554/eLife.18434

実験手法

X-RAY DIFFRACTION (1.852 Å)