University of Cambridge > Talks.cam > Seminars at the Department of Biochemistry > The Last of Us- Unravelling mechanisms of fungal micronutrient scavenging

The Last of Us- Unravelling mechanisms of fungal micronutrient scavenging

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Candida albicans causes more than 400,000 life-threatening, and half a billion mucosal infections annually. In response to infection, the host limits availability of essential micronutrients, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential for C. albicans pathogenicity, its limitation induces the secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is not known. Here, we present cryogenic electron microscopy structures of C. albicans Pra1 in its apo- and zinc-bound states. Our work reveals a hexameric ring-like assembly with multiple zinc binding sites. Through genetic studies, we show that the integrity of specific zinc binding sites is essential for C. albicans growth under zinc restriction. These data provide a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions, C. albicans zinc uptake, as well therapeutics development.

This talk is part of the Seminars at the Department of Biochemistry series.

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