8K9R

Cryo EM structure of the products-bound PGAP1(Bst1)-H443N from Chaetomium thermophilum

Summary for 8K9R

• Entry DOI: 10.2210/pdb8k9r/pdb
• EMDB information: 36996
• Descriptor: GPI inositol-deacylase,MCherry protein, Green fluorescent protein,Complement decay-accelerating factor, alpha-D-mannopyranose, ... (9 entities in total)
• Functional Keywords: bst1, glycosylphosphatidylinositol, gpi anchoring, gpi-ap, gpi-ap remodelase, integral membrane enzyme, lipase, lipid remodeling, membrane enzyme, membrane protein, nanodisc, pgap1, tgp, thermostable green fluorescence protein, transmembrane enzyme, triad enzyme.
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719) (Thermochaetoides thermophila); More
• Total number of polymer chains: 2
• Total formula weight: 193873.78

Authors

Li, T.,Hong, J.,Qu, Q.,Li, D. (deposition date: 2023-08-01, release date: 2023-12-20, Last modification date: 2024-10-23)

Primary citation

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, 15:8-8, 2024

PubMed 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.

PubMed: 38167496
DOI: 10.1038/s41467-023-44568-2

Experimental method

ELECTRON MICROSCOPY (2.68 Å)