Structural highlights
8k9r is a 2 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495, Homo sapiens, Psychromonas sp. B3M02 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | Electron Microscopy, Resolution 2.68Å |
| Ligands: | , , , , , , |
| 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hong J, Li T, Chao Y, Xu Y, Zhu Z, Zhou Z, Gu W, Qu Q, Li D. Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis. Nat Commun. 2024 Jan 2;15(1):8. PMID:38167496 doi:10.1038/s41467-023-44568-2
