Year: 2025
Type: article
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.
Source: Nature Communications
Authors: 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, Wei Dai
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Energy, U.S. Department of Health and Human Services, Rutgers, The State University of New Jersey, National Institutes of Health, Advanced Research Projects Agency - Energy, Institute on Ethnicity, Culture, and the Modern Experience, Rutgers University, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Office of Extramural Research, National Institutes of Health
Awards: G1734903128, Novel machine learning approaches for improving structural discrimination in cryo-electron tomography, G3488639887, G5536179168, Critical Factors Influencing Echinocandin Resistance in Candidaglabrata, G5788075268, A Bruker timsTOF HT mass spectrometer and nanoflow LC system to upgrade the proteomics facility at Rutgers-New Brunswick and Robert Wood Johnson Medical School, CAREER: PolyQ Proteins Phase Transition Induced by Lipid Vesicles, G6124856738, G6476786263, G6604512205, G6671297155, IN PLANTA SINGLE-MOLECULE IMAGING AND HOLOGRAPHIC FORCE SPECTROSCOPY TO STUDY REAL-TIME, MULTIMODAL TURNOVER DYNAMICS OF POLYSACCHARIDES AND ASSOCIATED CARBOHYDRATE METABOLITES, G7175986278, G7368923605, G8374068302, CAREER: Cryo-electron tomography derived multiscale integrative modeling of subcellular organization, Micropipette-based quantification of neuronal protein condensates in live cells, G9000034052, G9000138776, Understanding the viscoelasticity, surface tension, and membrane interactions of biomolecular condensates in live cells, G959131576, G992149501
OpenAlex ID: W4415147678