National Natural Science Foundation of China (NSFC)
82151215
中国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis. 著者: Yidan Xu / Tingting Li / Zixuan Zhou / Jingjing Hong / Yulin Chao / Zhini Zhu / Ying Zhang / Qianhui Qu / Dianfan Li / 要旨: Many eukaryotic receptors and enzymes rely on glycosylphosphatidylinositol (GPI) anchors for membrane localization and function. The transmembrane complex GPI-T recognizes diverse proproteins at a ...Many eukaryotic receptors and enzymes rely on glycosylphosphatidylinositol (GPI) anchors for membrane localization and function. The transmembrane complex GPI-T recognizes diverse proproteins at a signal peptide region that lacks consensus sequence and replaces it with GPI via a transamidation reaction. How GPI-T maintains broad specificity while preventing unintentional cleavage is unclear. Here, substrates- and products-bound human GPI-T structures identify subsite features that enable broad proprotein specificity, inform catalytic mechanism, and reveal a multilevel safeguard mechanism against its promiscuity. In the absence of proproteins, the catalytic site is invaded by a locally stabilized loop. Activation requires energetically unfavorable rearrangements that transform the autoinhibitory loop into crucial catalytic cleft elements. Enzyme-proprotein binding in the transmembrane and luminal domains respectively powers the conformational rearrangement and induces a competent cleft. GPI-T thus integrates various weak specificity regions to form strong selectivity and prevent accidental activation. These findings provide important mechanistic insights into GPI-anchored protein biogenesis.
超分子 #1: Complex of GPI-T with a chimeric GPI-anchored protein
超分子
名称: Complex of GPI-T with a chimeric GPI-anchored protein タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
理論値: 469 kDa/nm
+
分子 #1: UL16-binding protein 2,GFP-like fluorescent chromoprotein cFP484
分子
名称: UL16-binding protein 2,GFP-like fluorescent chromoprotein cFP484 タイプ: protein_or_peptide / ID: 1 詳細: A chimera proprotein containing the N- and C-terminal signal peptide of ULBP2, and a thermostable green fluorescence protein replacing the main part of ULBP2. コピー数: 1 / 光学異性体: LEVO