Structure of a fungal 1,3-β-glucan synthase

Abstract

Abstract1,3-β-Glucan is the major component of the fungal cell wall and is synthesized by 1,3-β-glucan synthase located in the plasma membrane, which is a molecular target of anti-fungal drugs echinocandins and the triterpenoid ibrexafungerp. In this study, we report the 3.0-Å resolution cryo-EM structure ofSaccharomyces cerevisiae1,3-β-glucan synthase, Fks1. 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 glucan-transporting channel. We found that two extracellular disulfide bonds are crucial for Fks1 enzymatic activity. Structural comparison between Fks1 and cellulose synthases and structure-guided mutagenesis studies provided novel insights into the molecular mechanisms of the fungal 1,3-β-glucan synthase.