Structural base for the transfer of GPI-anchored glycoproteins into fungal cell walls

Significance The synthesis and maturation of the cell wall are essential for fungal life. Factors involved in these processes provide a potential platform with side effect-free, antimycotic targets. A key step in cell-wall biogenesis is the transfer of GPI-anchored proteins from the plasma membrane to the glycan meshwork as catalyzed by Dfg5 enzymes. We characterize the structure of a member of the Dfg5 subfamily and provide insights into the architecture of the GPI-core glycan when bound to Dfg5 as supported by MD simulations and in vivo analysis in yeast. Our data let us propose a sorting mechanism at the fungal cell surface and set a base for structure-based drug development using this important cell-wall biosynthesis factor.