| Structural highlights
Disease
PIGU_HUMAN The disease is caused by variants affecting the gene represented in this entry.
Function
PIGU_HUMAN Component of the GPI transamidase complex, necessary for transfer of GPI to proteins (PubMed:34576938). May be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI.[1] [2]
Publication Abstract from PubMed
Glycosylphosphatidylinositol (GPI) molecules are complex glycophospholipids and serve as membrane anchors for tethering many proteins to the cell surface. Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by the transmembrane GPI transamidase (GPIT) complex, which is essential for maturation of the GPI-anchored proteins. The GPIT complex is known to be composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1. Here, we determined the structure of the human GPIT complex at a resolution of 3.1 A using single-particle cryo-EM, elucidating its overall assembly. The PIGK subunit functions as the catalytic component, in which we identified a C206-H164-N58 triad that is critical for the transamination reaction. Transmembrane helices constitute a widely opened cleft, which is located underneath PIGK, serving as a GPI substrate-binding site. The ubiquitin E3 ligase RNF121 is visualized at the back of the complex and probably serves as a quality control factor for the GPIT complex.
Structure of human glycosylphosphatidylinositol transamidase.,Zhang H, Su J, Li B, Gao Y, Liu M, He L, Xu H, Dong Y, Zhang XC, Zhao Y Nat Struct Mol Biol. 2022 Mar;29(3):203-209. doi: 10.1038/s41594-022-00726-6. , Epub 2022 Feb 14. PMID:35165458[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hong Y, Ohishi K, Kang JY, Tanaka S, Inoue N, Nishimura J, Maeda Y, Kinoshita T. Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins. Mol Biol Cell. 2003 May;14(5):1780-9. PMID:12802054 doi:10.1091/mbc.e02-12-0794
- ↑ Liu SS, Jin F, Liu YS, Murakami Y, Sugita Y, Kato T, Gao XD, Kinoshita T, Hattori M, Fujita M. Functional Analysis of the GPI Transamidase Complex by Screening for Amino Acid Mutations in Each Subunit. Molecules. 2021 Sep 8;26(18):5462. PMID:34576938 doi:10.3390/molecules26185462
- ↑ Zhang H, Su J, Li B, Gao Y, Liu M, He L, Xu H, Dong Y, Zhang XC, Zhao Y. Structure of human glycosylphosphatidylinositol transamidase. Nat Struct Mol Biol. 2022 Mar;29(3):203-209. PMID:35165458 doi:10.1038/s41594-022-00726-6
|
