6RY5

Crystal structure of Dfg5 from Chaetomium thermophilum in complex with alpha-1,6-mannobiose

6RY5 の概要

• エントリーDOI: 10.2210/pdb6ry5/pdb
• 分子名称: Mannan endo-1,6-alpha-mannosidase, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: transglycosidase, fungal cell wall, plasma membrane, gpi-anchor, gpi-cwp, hydrolase
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50118.80

構造登録者

Essen, L.-O.,Vogt, M.S. (登録日: 2019-06-10, 公開日: 2020-08-12, 最終更新日: 2020-09-16)

主引用文献

Vogt, M.S.,Schmitz, G.F.,Varon Silva, D.,Mosch, H.U.,Essen, L.O.
Structural base for the transfer of GPI-anchored glycoproteins into fungal cell walls.
Proc.Natl.Acad.Sci.USA, 117:22061-22067, 2020

PubMed Abstract: 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 GPI-anchored 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 GPI-anchored 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 GPI-core 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.

PubMed: 32839341
DOI: 10.1073/pnas.2010661117

実験手法

X-RAY DIFFRACTION (1.3 Å)