Structure of a fungal 1,3-β-glucan synthase
Chao-Ran Zhao, Zi-Long You, Dandan Chen, Jing Hang, Zhao-Bin Wang, Meng Ji, Le-Xuan Wang, Peng Zhao, Jie Qiao, Cai‐Hong Yun, Lin Bai
Abstract
1,3-β-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-β-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo–electron microscopy structure of Saccharomyces cerevisiae 1,3-β-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A–type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-β-glucan synthase.