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-Structure paper
Title | Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 5520, Year 2023 |
Publish date | Sep 8, 2023 |
Authors | Yidan Xu / Tingting Li / Zixuan Zhou / Jingjing Hong / Yulin Chao / Zhini Zhu / Ying Zhang / Qianhui Qu / Dianfan Li / |
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 ...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. |
External links | Nat Commun / PubMed:37684232 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.85 - 3.22 Å |
Structure data | EMDB-35575, PDB-8imx: EMDB-35576, PDB-8imy: |
Chemicals | ChemComp-Y01: ChemComp-MG: ChemComp-6OU: ChemComp-AJP: ChemComp-CA: ChemComp-NAG: ChemComp-LBN: ChemComp-80T: ChemComp-80Y: ChemComp-PA1: ChemComp-05E: ChemComp-81Q: |
Source |
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Keywords | MEMBRANE PROTEIN / cryo-EM / glycosylphosphatidylinositol / GPI / GPI anchored protein / GPI-AP / membrane protein complex / proprotein |