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Journal Article

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


Varón Silva,  Daniel
Daniel Varón Silva, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Vogt, M. S., Schmitz, G. F., Varón Silva, D., Mösch, H.-U., & Essen, L.-O. (2020). Structural base for the transfer of GPI-anchored glycoproteins into fungal cell walls. Proceedings of the National Academy of Sciences of the United States of America, 117(36), 22061-22067. doi:10.1073/pnas.2010661117.

Cite as: https://hdl.handle.net/21.11116/0000-0007-03E3-5
The correct distribution and trafficking of proteins are essential for
all organisms. Eukaryotes evolved a sophisticated trafficking system
which allows proteins to reach their destination within highly
compartmentalized cells. One eukaryotic hallmark is the attachment
of a glycosylphosphatidylinositol (GPI) anchor to C-terminal
ω-peptides, which are used as a zip code to guide a subset of
membrane-anchored proteins through the secretory pathway to
the plasma membrane. In fungi, the final destination of many GPIanchored
proteins is their outermost compartment, the cell wall.
Enzymes of the Dfg5 subfamily catalyze the essential transfer of
GPI-anchored substrates from the plasma membrane to the cell
wall and discriminate between plasma membrane-resident GPIanchored
proteins and those transferred to the cell wall (GPI-CWP).
We solved the structure of Dfg5 from a filamentous fungus and
used in crystallo glycan fragment screening to reassemble the GPIcore
glycan in a U-shaped conformation within its binding pocket.
The resulting model of the membrane-bound Dfg5•GPI-CWP complex
is validated by molecular dynamics (MD) simulations and
in vivo mutants in yeast. The latter show that impaired transfer
of GPI-CWPs causes distorted cell-wall integrity as indicated by
increased chitin levels. The structure of a Dfg5•β1,3-glycoside complex
predicts transfer of GPI-CWP toward the nonreducing ends of
acceptor glycans in the cell wall. In addition to our molecular model
for Dfg5-mediated transglycosylation, we provide a rationale for
how GPI-CWPs are specifically sorted toward the cell wall by using
GPI-core glycan modifications.