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-Structure paper
Title | Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 2617, Year 2022 |
Publish date | May 12, 2022 |
Authors | Yidan Xu / Guowen Jia / Tingting Li / Zixuan Zhou / Yitian Luo / Yulin Chao / Juan Bao / Zhaoming Su / Qianhui Qu / Dianfan Li / |
PubMed Abstract | Eukaryotic cells are coated with an abundance of glycosylphosphatidylinositol anchor proteins (GPI-APs) that play crucial roles in fertilization, neurogenesis, and immunity. The removal of a ...Eukaryotic cells are coated with an abundance of glycosylphosphatidylinositol anchor proteins (GPI-APs) that play crucial roles in fertilization, neurogenesis, and immunity. The removal of a hydrophobic signal peptide and covalent attachment of GPI at the new carboxyl terminus are catalyzed by an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GPI-T at a global 2.53-Å resolution, revealing an equimolar heteropentameric assembly. Structure-based mutagenesis suggests a legumain-like mechanism for the recognition and cleavage of proprotein substrates, and an endogenous GPI in the structure defines a composite cavity for the lipid substrate. This elongated active site, stemming from the membrane and spanning an additional ~22-Å space toward the catalytic dyad, is structurally suited for both substrates which feature an amphipathic pattern that matches this geometry. Our work presents an important step towards the mechanistic understanding of GPI-AP biosynthesis. |
External links | Nat Commun / PubMed:35551457 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.53 Å |
Structure data | EMDB-32582, PDB-7wld: |
Chemicals | ChemComp-Y01: ChemComp-AJP: ChemComp-BJR: ChemComp-PEE: ChemComp-CA: ChemComp-P5S: ChemComp-NAG: ChemComp-CLR: ChemComp-05E: ChemComp-PA1: ChemComp-CDL: ChemComp-DKB: ChemComp-06O: |
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Keywords | TRANSFERASE / GPI anchoring / GPI-AP / glycosylphosphatidylinositol transamidase / GPI transamidase / membrane protein complex |