Molecular landscape of the fungal plasma membrane and implications for antifungal action
Jennifer Jiang,
Mikhail V. Keniya,
Anusha Puri,
Xueying Zhan,
Jeff Cheng,
Huan Wang,
Gigi Lin,
Yun-Kyung Lee,
Nora Jaber,
Caifeng Zhao,
Cynthia Pang,
Yasmine Hassoun,
Haiyan Zheng,
Erika Shor,
Zheng Shi,
Sang-Hyuk Lee,
Min Xu,
David S. Perlin () and
Wei Dai ()
Additional contact information
Jennifer Jiang: The State University of New Jersey
Mikhail V. Keniya: Hackensack Meridian Health-Center for Discovery and Innovation
Anusha Puri: The State University of New Jersey
Xueying Zhan: Carnegie Mellon University
Jeff Cheng: The State University of New Jersey
Huan Wang: The State University of New Jersey
Gigi Lin: City University of New York-Hunter College
Yun-Kyung Lee: The State University of New Jersey
Nora Jaber: The State University of New Jersey
Caifeng Zhao: The State University of New Jersey
Cynthia Pang: The State University of New Jersey
Yasmine Hassoun: Hackensack Meridian Health-Center for Discovery and Innovation
Haiyan Zheng: The State University of New Jersey
Erika Shor: Hackensack Meridian Health-Center for Discovery and Innovation
Zheng Shi: The State University of New Jersey
Sang-Hyuk Lee: The State University of New Jersey
Min Xu: Carnegie Mellon University
David S. Perlin: Hackensack Meridian Health-Center for Discovery and Innovation
Wei Dai: The State University of New Jersey
Nature Communications, 2025, vol. 16, issue 1, 1-14
Abstract:
Abstract Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their native structure and spatial distribution remain poorly characterized. Herein, we employ an integrative approach to investigate the organization of plasma membrane protein complexes in Candida glabrata, focusing on two abundant and essential membrane proteins, the β-(1,3)-glucan synthase (GS) and the proton pump Pma1. We show that treatment with caspofungin, an echinocandin antifungal that targets GS, disrupts the native distribution of membrane protein complexes and alters membrane biophysical properties. Perturbation of the sphingolipid biosynthesis further modulates drug susceptibility, revealing that the lipid environment plays an integral role in membrane protein organization and GS-echinocandin interactions. Our work highlights the importance of characterizing membrane proteins in their native context to understand their functions and inform the development of novel antifungal therapies.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64171-x
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DOI: 10.1038/s41467-025-64171-x
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