β-1,3-葡聚糖合酶FKS1-Rho1复合物的冷冻电镜结构

Cryo-EM structure of the β-1,3-glucan synthase FKS1-Rho1 complex.

作者信息

Li Jialu, Liu Huayi, Li Jian, Liu Juxiu, Dai Xinli, Zhu Angqi, Xiao Qingjie, Qian Wenyu, Li Honghao, Guo Li, Yan Chuangye, Deng Dong, Luo Yunzi, Wang Xiang

机构信息

Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.

Frontiers Science Center for Synthetic Biology (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

出版信息

Nat Commun. 2025 Feb 28;16(1):2054. doi: 10.1038/s41467-025-57152-7.

DOI:10.1038/s41467-025-57152-7

PMID:40021629

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11871024/

Abstract

β-1,3 Glucan synthase (GS) is essential for fungal cell wall biosynthesis. The GS holoenzyme comprises the glycosyltransferase FKS1 and its regulatory factor Rho1, a small GTPase. However, the mechanism by which Rho1 activates FKS1 in a GTP-dependent manner remains unclear. Here, we present two cryo-EM structures of FKS1, apo and in complex with Rho1. FKS1 adopts a cellulose synthase-like conformation. The interaction between Rho1 and FKS1 is enhanced in the presence of GTPγS. Rho1 is positioned within a pocket between the glycosyltransferase domain of FKS1 (GT domain) and the transmembrane helix spanning TM7-15. Comparison of the two structures reveals extensive conformational changes within FKS1. These alterations suggest that Rho1's GTP/GDP cycling may act as a molecular pump, promoting a dynamic transition between the resting and active states of FKS1. Notably, Rho1 triggers FKS1 conformational changes that may push the growing glucan chain into FKS1's transmembrane channel, thereby facilitating β-1,3-glucan elongation.

摘要

β-1,3-葡聚糖合酶（GS）对于真菌细胞壁的生物合成至关重要。GS全酶由糖基转移酶FKS1及其调节因子Rho1（一种小GTP酶）组成。然而，Rho1以GTP依赖的方式激活FKS1的机制仍不清楚。在此，我们展示了FKS1的两种冷冻电镜结构，一种是无配体的，另一种是与Rho1结合的复合物。FKS1呈现出类似纤维素合酶的构象。在存在GTPγS的情况下，Rho1与FKS1之间的相互作用增强。Rho1位于FKS1的糖基转移酶结构域（GT结构域）和跨膜螺旋TM7 - 15之间的一个口袋内。两种结构的比较揭示了FKS1内广泛的构象变化。这些改变表明Rho1的GTP/GDP循环可能充当分子泵，促进FKS1在静止状态和活性状态之间的动态转变。值得注意的是，Rho1触发FKS1的构象变化，这可能将正在生长的葡聚糖链推入FKS1的跨膜通道，从而促进β-1,3-葡聚糖的延伸。