Structure of human glycosylphosphatidylinositol transamidase
Hongwei Zhang, Jiawei Su, Bin Li, Yiwei Gao, Mengran Liu, Lingli He, Hao Xu, Yanli Dong, Xuejun Cai Zhang & Yan Zhao
Abstract
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?? 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.
附件下载：
Structure of human glycosylphosphatidylinositol transamidase, Nat Struct Mol Biol, 14 Feb 2022
Nature Structural & Molecular Biology, 14 February, 2022, DOI：https://doi.org/10.1038/s41594-022-00726-6
Structure of human glycosylphosphatidylinositol transamidase
Hongwei Zhang, Jiawei Su, Bin Li, Yiwei Gao, Mengran Liu, Lingli He, Hao Xu, Yanli Dong, Xuejun Cai Zhang & Yan Zhao
Abstract
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?? 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.
文章链接：https://www.nature.com/articles/s41594-022-00726-6
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