Structure of a fungal 1,3-β-glucan synthase
Open accessPublished version of a preprint
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.
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References 49 · Cited by 75
- Authors
- Zhao, C.-R., You, Z.-L., Chen, D.-D., Hang, J., Wang, Z.-B., Ji, M., Wang, L.-X., Zhao, P., Qiao, J., Yun, C.-H., & Bai, L.
- Affiliations
- Peking University (CN)
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, China.
- Corresponding author
- Zhao, Chao-Ran
- You, Zi-Long
- Hang, Jing
- Qiao, Jie
- Yun, Cai-Hong
- Bai, Lin
- ORCID
- Venue
- Science Advances
- Published
- 2023-09-15
- Volume
- 9
- Issue
- 37
- Pages
- eadh7820-eadh7820
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC10499315
- OpenAlex
- W4386719062
- Cited by
- 75
- References
- 49
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 13 · 2021: 1
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (32171212, 973 Program, 82071658, 32071207)
- Chinese Academy of Sciences
- Peking University
- Beijing Nova Program (20220484160, Z201100006820010)
- National Key Research and Development Program of China (2018YFC1004403, 2022YFC2702904, 2012CB917202)
- Fundamental Research Funds for the Central Universities
- Institute of Biophysics, Chinese Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Polysaccharides and Plant Cell Walls
- Keywords
- beta-1,3-glucan synthase, FKS1, Saccharomyces cerevisiae, fungal cell wall, plasma membrane enzymes, cryo-EM structure, transmembrane channels, disulfide bonds, echinocandins, ibrexafungerp, antifungal drug targets, enzyme mechanism
- MeSH terms
- Antifungal Agents, Catalysis, Glucosyltransferases, Cryoelectron Microscopy, beta-Glucans
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