8IMX

Cryo-EM structure of GPI-T with a chimeric GPI-anchored protein

8IMX の概要

• エントリーDOI: 10.2210/pdb8imx/pdb
• 関連するPDBエントリー: 7W72 7WLD
• EMDBエントリー: 32336 32582 35575
• 分子名称: UL16-binding protein 2,GFP-like fluorescent chromoprotein cFP484, MAGNESIUM ION, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate, ... (20 entities in total)
• 機能のキーワード: cryo-em, glycosylphosphatidylinositol, gpi, gpi anchored protein, gpi-ap, membrane protein complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 483826.37

構造登録者

Xu, Y.,Li, T.,Qu, Q.,Li, D. (登録日: 2023-03-07, 公開日: 2023-08-16, 最終更新日: 2025-07-23)

主引用文献

Xu, Y.,Li, T.,Zhou, Z.,Hong, J.,Chao, Y.,Zhu, Z.,Zhang, Y.,Qu, Q.,Li, D.
Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis.
Nat Commun, 14:5520-5520, 2023

PubMed Abstract: 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.

PubMed: 37684232
DOI: 10.1038/s41467-023-41281-y

実験手法

ELECTRON MICROSCOPY (2.85 Å)