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Glycosylphosphatidylinositols (GPIs) are a class of complex glycolipids composed of mannose, glucosamine, phosphoethanolamine, and inositol phospholipids
.
It can be covalently linked to the carboxyl terminus of some proteins, anchoring it to the outer leaflet of the cytoplasmic membrane for biological functions
The biosynthesis of GPI-anchored proteins is a type of protein post-translational modification that is widely present in all eukaryotes, and the biochemical reactions involved in this modification process are conserved, including three main steps: (1) Endoplasmic GPI molecules are synthesized on the omentum; (2) under the action of GPI transamidase (GPIT), the carboxyl-terminal (C-terminal) signal peptide of GPI-AP precursor protein (ProGPI-AP) is cleaved and covalently linked to GPI molecules , to form GPI-AP; (3) GPI-AP is transported to the cell membrane through the Golgi apparatus after further processing and maturation
.
The GPI transamidase complex is a key catalytic enzyme for the second step of GPI-anchored protein biosynthesis and consists of five subunits, including PIGK, PIGU, PIGT, PIGS, and GPAA1
On February 15, 2022, Zhao Yan's research group from the Institute of Biophysics, Chinese Academy of Sciences published an article entitled "Structure of human glycosylphosphatidylinositol transamidase" in the journal " Nature Structural & Molecular Biology ", which analyzed the human glycosylphosphatidylinositol for the first time.
The 3.
1 Å high-resolution structure of the transamidase; at the same time, the researchers also verified the enzyme by modifying the green fluorescent protein GFP, using CRISPR/Cas9 gene editing technology, flow cytometry and confocal microscopy imaging techniques, etc.
The catalytic active site and important amino acid residues that exert catalytic activity
.
Figure 1: ab.
The overall structure of the GPIT complex; c.
The structure of a single subunit of the GPIT complex; d.
The activity of the GPIT complex was verified by confocal microscopy
.
The overall structure of GPI transamidase resembles a jumping dolphin
.
In the transmembrane helix region, the PIGU subunit interacts with the transmembrane helices of GPAA1, PIGK, PIGT, and PIGS, respectively, thereby mediating the assembly of the complex; in the endoplasmic reticulum cavity, the soluble domains of the catalytic subunit PIGK are respectively It interacts with other subunits through disulfide bonds, electrostatic interactions and van der Waals forces to form a stable complex structure and perform catalytic functions
Interestingly, structural analysis revealed that the GPIT complex could interact with another unknown protein composed of six transmembrane helices
.
The results of mass spectrometry showed that the E3 ubiquitin ligase RNF121 was abundant in the purified GPIT complex samples and had six transmembrane helices
Researcher Zhao Yan from the Institute of Biophysics, Chinese Academy of Sciences is the corresponding author of this research paper
.
Zhang Hongwei, Su Jiawei and Li Bin, doctoral candidates of the Institute of Biophysics, are the co-first authors of this paper
Article link: https:// align="justify">
(Contributed by Zhao Yan's research group)
