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TitleMolecular landscape of the fungal plasma membrane and implications for antifungal action.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9125, Year 2025
Publish dateOct 14, 2025
AuthorsJennifer 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 / Wei Dai /
PubMed AbstractFungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their native structure and spatial distribution remain poorly characterized. Herein, we employ an ...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.
External linksNat Commun / PubMed:41087328 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-45105: Cryo-electron tomography of Candida glabrata plasma membrane
Method: EM (tomography)

EMDB-45106: Cryo-electron tomography of plasma membranes generated from caspofungin-treated Candida glabrata spheroplasts
Method: EM (tomography)

Source
  • Nakaseomyces glabratus (fungus)

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