タンパク質複合体構造の進化の歴史は繰り返す～大規模ゲノム情報からの偶然の発見をもとに実験で証明～

2025-09-22 東京大学

融合酵素AdhEとBdhEでは複合体構造が収斂進化している^{*9/22図差し替え}

<関連情報>

• https://www.s.u-tokyo.ac.jp/ja/press/10922/
• https://www.nature.com/articles/s41467-025-63898-x

収斂的遺伝子融合に続くタンパク質構造進化の再現性 Repeatability of protein structural evolution following convergent gene fusions

Naoki Konno,Keita Miyake,Satoshi Nishino,Kimiho Omae,Haruaki Yanagisawa,Saburo Tsuru,Yuki Nishimura,Masahide Kikkawa,Chikara Furusawa & Wataru Iwasaki
Nature Communications  Published:22 September 2025
DOI:https://doi.org/10.1038/s41467-025-63898-x

Abstract

Convergent evolution of proteins provides insights into repeatability of genetic adaptation. While local convergence of proteins at residue or domain level has been characterized, global structural convergence by inter-domain/molecular interactions remains largely unknown. Here we present structural convergent evolution on fusion enzymes of aldehyde dehydrogenases (ALDHs) and alcohol dehydrogenases (ADHs). We discover BdhE (bifunctional dehydrogenase E), an enzyme clade that emerged independently from the previously known AdhE family through distinct gene fusion events. AdhE and BdhE show shared enzymatic activities and non-overlapping phylogenetic distribution, suggesting common functions in different species. Cryo-electron microscopy reveals BdhEs form donut-like homotetramers, contrasting AdhE’s helical homopolymers. Intriguingly, despite distinct quaternary structures and < 30% amino acid sequence identity, both enzymes forms resemble dimeric structure units by ALDH-ADH interactions via convergently elongated loop structures. These findings suggest convergent gene fusions recurrently led to substrate channeling evolution to enhance two-step reaction efficiency. Our study unveils structural convergence at inter-domain/molecular level, expanding our knowledges on patterns behind molecular evolution exploring protein structural universe.