9UTU

Structure of Fks1 in complex with YMR295C

9UTU の概要

• エントリーDOI: 10.2210/pdb9utu/pdb
• EMDBエントリー: 37602 64501
• 分子名称: 1,3-beta-glucan synthase component FKS1, YMR295C isoform 1, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 237310.14

構造登録者

Li, J.L.,Zhu, A.Q.,Wang, X.,Yan, C.Y.,Deng, D. (登録日: 2025-05-05, 公開日: 2025-12-17, 最終更新日: 2026-01-28)

主引用文献

Li, J.,Li, J.,Zhu, A.,Dai, X.,Liu, J.,Liu, H.,Xia, Z.,Dong, Y.,Qian, W.,Dai, L.,Guo, L.,Yan, C.,Deng, D.,Luo, Y.,Wang, X.
Structural-guided identification of two modulators of beta-1,3-glucan synthase FKS1.
Nat Commun, 17:591-591, 2025

PubMed Abstract: FKS1 is a β-1,3-glucan synthase critical for fungal cell wall formation and a target for antifungal drugs such as echinocandin and ibrexafungerp. However, the mechanisms regulating FKS1 activity remain largely unknown. Here, we reveal that transfer RNA (tRNA) acts as an endogenous inhibitor, whereas GSR1 functions as a stabilizer of FKS1. The cryo-EM structure of FKS1 adopts a tRNA-mediated homodimer configuration, representing a quiescent state of β-1,3-glucan synthase. Unexpectedly, the copurified endogenous tRNA is identified as a potent inhibitor that suppresses FKS1 activity. Moreover, high-resolution cryo-EM density analysis enable the identification of GSR1 as an additional binding partner of FKS1. Mutagenesis experiments confirm the interaction between FKS1 and GSR1. Evolutionarily conserved GSR1 is found to increase the stability of FKS1 in β-1,3-glucan biosynthesis. Collectively, our findings identify both tRNA and GSR1 as intrinsic modulators of β-1,3-glucan biosynthesis, thereby providing opportunities for the further development of FKS1-targeted antifungal drugs.

PubMed: 41354657
DOI: 10.1038/s41467-025-67293-4

実験手法

ELECTRON MICROSCOPY (2.72 Å)