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TitleMolecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 2617, Year 2022
Publish dateMay 12, 2022
AuthorsYidan Xu / Guowen Jia / Tingting Li / Zixuan Zhou / Yitian Luo / Yulin Chao / Juan Bao / Zhaoming Su / Qianhui Qu / Dianfan Li /
PubMed AbstractEukaryotic 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 linksNat Commun / PubMed:35551457 / PubMed Central
MethodsEM (single particle)
Resolution2.53 Å
Structure data

EMDB-32582, PDB-7wld:
Cryo-EM structure of the human glycosylphosphatidylinositol transamidase complex at 2.53 Angstrom resolution
Method: EM (single particle) / Resolution: 2.53 Å

Chemicals

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-AJP:
Digitonin / detergent*YM

ChemComp-BJR:
(4S,7R)-7-[(hexadecanoyloxy)methyl]-4-hydroxy-N,N,N-trimethyl-4,9-dioxo-3,5,8-trioxa-4lambda~5~-phosphahexacosan-1-aminium

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

ChemComp-CA:
Unknown entry

ChemComp-P5S:
O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CLR:
CHOLESTEROL

ChemComp-05E:
2-azanylethyl [(2~{S},3~{S},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-2,4,5-tris(oxidanyl)oxan-3-yl] hydrogen phosphate

ChemComp-PA1:
2-amino-2-deoxy-alpha-D-glucopyranose

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-DKB:
[(2R)-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] octadecanoate

ChemComp-06O:
[(2~{R})-1-hexadecanoyloxy-3-[[(1~{S},2~{R},3~{R},4~{S},5~{S},6~{R})-2-hexadecanoyloxy-3,4,5,6-tetrakis(oxidanyl)cyclohexyl]oxy-oxidanyl-phosphoryl]oxy-propan-2-yl] (9~{Z},11~{Z})-octadeca-9,11-dienoate

Source
  • homo sapiens (human)
KeywordsTRANSFERASE / GPI anchoring / GPI-AP / glycosylphosphatidylinositol transamidase / GPI transamidase / membrane protein complex

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