Proteomics

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A novel structure of GPI anchored proteins


ABSTRACT: GPI anchors many proteins to the cell surface. GPI precursor has three mannoses, all of which are modified by ethanolamine-phosphate (EthN-P). It has been believed that EthN-P on the third mannose is always used as a bridge to the protein and EthN-P on the second mannose is removed after GPI is attached to the protein. Based on the finding that PIGB-knockout cells lacking the third mannose and PIGO-knockout cells lacking EthN-P linked to the third mannose expressed low levels of CD59 and DAF, GPI-APs and that those residual GPI-APs were lost by further knockout of PIGG. Using mass-spectrometry we determined that CD59 expressed on PIGB-knockout cells is attached to GPI via EthN-P linked to the second mannose. This linkage structure is also found in wild type cells. Our data modifies the current view of GPI anchors and provides mechanistic basis of inherited GPI deficiency caused by PIGG mutations.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Epithelial Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Yoshiko Murakami  

LAB HEAD: Taroh Kinoshita

PROVIDER: PXD021996 | Pride | 2022-05-31

REPOSITORIES: Pride

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Publications

Ethanolamine-phosphate on the second mannose is a preferential bridge for some GPI-anchored proteins.

Ishida Mizuki M   Maki Yuta Y   Ninomiya Akinori A   Takada Yoko Y   Campeau Philippe P   Kinoshita Taroh T   Murakami Yoshiko Y  

EMBO reports 20220523 7


Glycosylphosphatidylinositols (GPIs) are glycolipids that anchor many proteins (GPI-APs) on the cell surface. The core glycan of GPI precursor has three mannoses, which in mammals, are all modified by ethanolamine-phosphate (EthN-P). It is postulated that EthN-P on the third mannose (EthN-P-Man3) is the bridge between GPI and the protein and the second (EthN-P-Man2) is removed after GPI-protein attachment. However, EthN-P-Man2 may not be always transient, as mutations of PIGG, the enzyme that tr  ...[more]

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