ArticleNature communications2024
Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Mechanisms of Quality Control in GPI-Anchored Proteins: The Central Role of the Lipid Anchor.International journal of molecular sciences · 2026Review
- Th17-related genes PGAP1 and TMBIM1 serve as potential diagnostic and predictive biomarkers in systemic sclerosis: bioinformatic identification and murine model validation.Clinical rheumatology · 2026Article
- Biosynthesis of GPI anchored proteins, its deficiencies and treatment.Journal of human genetics · 2025Review
- Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells.Science advances · 2025Article
- Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.Nature structural & molecular biology · 2025Article
- Stressors-induced cognitive dysfunction during aging: mechanisms and future challenges.Frontiers in aging neuroscience · 2025Article
- Structure-based design of covalent nanobody binders for a thermostable green fluorescence protein.Acta biochimica et biophysica Sinica · 2024Article
- Hereditary Spastic Paraplegia Associated with Ultra-Rare Variant Enrichment Encompassing the SYNE1, CAPN1 and PGAP1 Genes.Cerebellum (London, England) · 2024Article
- Inherited glycosylphosphatidylinositol deficiency: a review from molecular and clinical perspectives.Acta biochimica et biophysica Sinica · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
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 Å), 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.