7WLD

Cryo-EM structure of the human glycosylphosphatidylinositol transamidase complex at 2.53 Angstrom resolution

7WLD の概要

• エントリーDOI: 10.2210/pdb7wld/pdb
• EMDBエントリー: 32582
• 分子名称: Glycosylphosphatidylinositol anchor attachment 1 protein, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, CALCIUM ION, ... (19 entities in total)
• 機能のキーワード: gpi anchoring, gpi-ap, glycosylphosphatidylinositol transamidase, gpi transamidase, membrane protein complex, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 451005.48

構造登録者

Xu, Y.,Li, T.,Luo, Y.,Chao, Y.,Jia, G.,Zhou, Z.,Su, Z.,Qu, Q.,Li, D. (登録日: 2022-01-13, 公開日: 2022-04-27, 最終更新日: 2022-06-01)

主引用文献

Xu, Y.,Jia, G.,Li, T.,Zhou, Z.,Luo, Y.,Chao, Y.,Bao, J.,Su, Z.,Qu, Q.,Li, D.
Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins.
Nat Commun, 13:2617-2617, 2022

PubMed Abstract: 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.

PubMed: 35551457
DOI: 10.1038/s41467-022-30250-6

実験手法

ELECTRON MICROSCOPY (2.53 Å)