National Natural Science Foundation of China (NSFC)
82151215
中国
引用
ジャーナル: Nat Commun / 年: 2024 タイトル: Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis. 著者: Jingjing Hong / Tingting Li / Yulin Chao / Yidan Xu / Zhini Zhu / Zixuan Zhou / Weijie Gu / Qianhui Qu / Dianfan Li / 要旨: The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates ...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.
名称: GPI inositol-deacylase,MCherry protein / タイプ: protein_or_peptide / ID: 1 詳細: Residues 1-1186 is GPI inositol-deacylase (Uniprot ID G0S652) with a H443N mutation. Residues 1187-1200 is the linker with a 3 C protease digestion site. Residues 1201-1435 is a fused mCherry ...詳細: Residues 1-1186 is GPI inositol-deacylase (Uniprot ID G0S652) with a H443N mutation. Residues 1187-1200 is the linker with a 3 C protease digestion site. Residues 1201-1435 is a fused mCherry protein (Uniprot ID A0A366VY15 with the following four mutations that extend its fluorescence lifetime: W148S, I166V, Q168Y and I202R). Residues 1436-1447 is the linker with a His tag. コピー数: 1 / 光学異性体: LEVO EC番号: 加水分解酵素; エステル加水分解酵素
UniProtKB: GPI inositol-deacylase, Uncharacterized protein
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分子 #2: Green fluorescent protein,Complement decay-accelerating factor
分子
名称: Green fluorescent protein,Complement decay-accelerating factor タイプ: protein_or_peptide / ID: 2 詳細: Residues 1-6 is a linker. Residues 7-231 is a thermostable green fluorescent protein (PDB entry 4TZA, residue 5-229). Residues 232-263 is a linker with an expression tag. Residues 264-272 is ...詳細: Residues 1-6 is a linker. Residues 7-231 is a thermostable green fluorescent protein (PDB entry 4TZA, residue 5-229). Residues 232-263 is a linker with an expression tag. Residues 264-272 is human CD55 (Uniprot ID P08174, residue P345-T353). コピー数: 1 / 光学異性体: LEVO