AI Article Synopsis

  • Fungal plasma membrane proteins are crucial targets for antifungal treatments, but their structures and distributions are not well understood.
  • This study uses techniques like cryo-electron tomography and live cell imaging to investigate the organization of essential membrane proteins, GS and Pma1, finding they are unevenly spread in the plasma membrane.
  • The research reveals that the antifungal drug caspofungin alters the distribution of these proteins, suggesting a new model for how echinocandin drugs work by affecting the plasma membrane environment of fungal cells.

Article Abstract

Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their structure and spatial distribution in the native context remain poorly characterized. Herein, we employ an integrative multimodal approach to elucidate the structural and functional organization of plasma membrane protein complexes in , focusing on prominent and essential membrane proteins, the polysaccharide synthase β-(1,3)-glucan synthase (GS) and the proton pump Pma1. Cryo-electron tomography (cryo-ET) and live cell imaging reveal that GS and Pma1 are heterogeneously distributed into distinct plasma membrane microdomains. Treatment with caspofungin, an echinocandin antifungal that targets GS, alters the plasma membrane and disrupts the native distribution of GS and Pma1. Based on these findings, we propose a model for echinocandin action that considers how drug interactions with the plasma membrane environment lead to inhibition of GS. Our work underscores the importance of interrogating the structural and dynamic characteristics of fungal plasma membrane proteins to understand function and facilitate precisely targeted development of novel antifungal therapies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160696PMC
http://dx.doi.org/10.1101/2024.05.29.596243DOI Listing

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