菌類がステロールにアミノ酸を付ける仕組みを解明～ tRNAを使って脂質を修飾する酵素ErdSの構造と働きを解明～

2026-05-28 東京大学

ErdSによるtRNA依存的なErg-Asp合成

＜関連情報＞

• https://www.s.u-tokyo.ac.jp/ja/press/11148/
• https://www.nature.com/articles/s41467-026-73135-8

エルゴステリルアスパラギン酸シンターゼの構造解析により、捕捉されたtRNAがアミノアシル化ステロールの合成において、まるで義肢のような振り子のように利用される仕組みが明らかになった Structure of ergosteryl-aspartate synthase reveals how an entrapped tRNA is used like a prosthetic swinging arm in the synthesis of aminoacylated sterols

Hanako Murayama,Nathaniel Yakobov,Nassira Mahmoudi,Sasha Legrosdidier,Nicolas Fournier,Solène Zuttion,Kanata Matsumoto,Michihiro Nishimura,Jingwei Ji,Bruno Senger,Laurence Huck,Howard B. Gamper,Yoshiaki Kise,Ralph E. Kleiner,Mathieu Frechin,Ya-Ming Hou,Hubert D. Becker,Yuzuru Itoh,Frédéric Fischer & Osamu Nureki
Nature Communications  Published:28 May 2026
DOI:https://doi.org/10.1038/s41467-026-73135-8

Abstract

Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNA^Asp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNA^Asp undergoes a large displacement to reach the aa-tRNA transfer active site, while the tRNA elbow is clamped by a long extension an N-terminal α-helix. The present structural and mutational analyses demonstrate that domain fusion, dynamic repositioning, and tRNA-mediated substrate handover underlie the multifunctional catalytic efficiency of ErdS and participates in Erg-Asp synthesis independently from protein synthesis. These findings elucidate the regulatory mechanism of tRNA-dependent sterol modification and provide insights into fungal membrane dynamics, highlighting potential targets for antifungal therapies.