8k9q

Cryo-EM structure of the GPI inositol-deacylase (PGAP1/Bst1) from Chaetomium thermophilum

spinqualitylabelsall models 8k9q, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8k9q is a 1 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.84Å Ligands: D39, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0S652_CHATD Involved in inositol deacylation of GPI-anchored proteins which plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins.[ARBA:ARBA00003496][RuleBase:RU365011] Publication Abstract from PubMed The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66-2.84 A), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling. Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis.,Hong J, Li T, Chao Y, Xu Y, Zhu Z, Zhou Z, Gu W, Qu Q, Li D Nat Commun. 2024 Jan 2;15(1):8. doi: 10.1038/s41467-023-44568-2. PMID:38167496 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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