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bioRxiv · 10.1101/2023.03.19.532754

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

Zhao, C.-R.·You, Z.-L.·Chen, D.-d.·Hang, J.·Wang, Z.-B.·Wang, L.-X.·Zhao, P.·Qiao, J.·Yun, C.-H.·Bai, L.
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Abstract

1,3-{beta}-Glucan is the major component of the fungal cell wall and is synthesized by 1,3-{beta}-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-[A] resolution cryo-EM structure of Saccharomyces cerevisiae 1,3-{beta}-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-{beta}-glucan synthase.

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Zhao, C.-R., You, Z.-L., Chen, D.-d., Hang, J., Wang, Z.-B., Wang, L.-X., Zhao, P., Qiao, J., Yun, C.-H., Bai, L.. 2023-03-20. Structure of a fungal 1,3-β-glucan synthase. https://doi.org/10.1101/2023.03.19.532754

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