8K9T

Cryo-EM structure of the products-bound PGAP1(Bst1)-S327A from Chaetonium thermophilum

8K9T の概要

• エントリーDOI: 10.2210/pdb8k9t/pdb
• EMDBエントリー: 36997
• 分子名称: GPI inositol-deacylase,MCherry protein, Green fluorescent protein,Complement decay-accelerating factor, PALMITIC ACID, ... (9 entities in total)
• 機能のキーワード: 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.
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719) (Thermochaetoides thermophila); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 194288.47

構造登録者

Li, T.,Hong, J.,Qu, Q.,Li, D. (登録日: 2023-08-01, 公開日: 2023-12-20, 最終更新日: 2025-07-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.66 Å)