9OHL

TRMT112-METTL5 bound to SAM and FWG-33B

これはPDB形式変換不可エントリーです。

9OHL の概要

• エントリーDOI: 10.2210/pdb9ohl/pdb
• 分子名称: rRNA N(6)-adenosine-methyltransferase METTL5, Multifunctional methyltransferase subunit TRM112-like protein, S-ADENOSYLMETHIONINE, ... (6 entities in total)
• 機能のキーワード: trna methyltransferase 112 homolog, methyltransferase-like protein 5, stereoselective probe, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38885.37

構造登録者

Goetzke, F.W.,Bernard, S.M. (登録日: 2025-05-05, 公開日: 2025-06-11, 最終更新日: 2025-06-18)

主引用文献

Goetzke, F.W.,Bernard, S.M.,Ju, C.W.,Pollock, J.,DeMeester, K.E.,Gross, J.,Simon, G.M.,He, C.,Melillo, B.,Cravatt, B.F.
Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.
Biorxiv, 2025

PubMed Abstract: Adaptors serve as hubs to regulate diverse protein complexes in cells. This multitude of functions can complicate the study of adaptors, as their genetic disruption may simultaneously impair the activities of several compositionally distinct complexes (or adaptor 'complexoforms'). Here we describe the chemical proteomic discovery of bicyclopyrrolidine acrylamide stereoprobes that react with cysteine-100 (C100) of the methyltransferase (MT) adaptor TRMT112 in human cells. Curiously, the stereoprobes showed negligible reactivity with uncomplexed recombinant TRMT112, and we found that this interaction was restored excluively in the presence of METTL5, but not other MTs. A co-crystal structure revealed stereoprobe binding to a composite pocket proximal to C100 of TRMT112 that is templated by METTL5 and absent in other TRMT112:MT complexes. Structural rearrangements promoted by stereoprobe binding in turn lead to allosteric agonism of METTL5, thus revealing how covalent ligands targeting a pleiotropic adaptor can confer partner-specific functional effects through reactivity with a single complexoform.

PubMed: 40475643
DOI: 10.1101/2025.05.25.655995

実験手法

X-RAY DIFFRACTION (1.286 Å)