7S06

Cryo-EM structure of human GlcNAc-1-phosphotransferase A2B2 subcomplex

7S06 の概要

• エントリーDOI: 10.2210/pdb7s06/pdb
• EMDBエントリー: 24785
• 分子名称: N-acetylglucosamine-1-phosphotransferase subunits alpha/beta, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: glcnac-1-phosphotransferase, lysosomal hydrolases, mannose 6-phosphate trafficking pathway, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 272599.85

構造登録者

Li, H.,Li, H. (登録日: 2021-08-30, 公開日: 2022-03-30, 最終更新日: 2024-11-06)

主引用文献

Li, H.,Lee, W.S.,Feng, X.,Bai, L.,Jennings, B.C.,Liu, L.,Doray, B.,Canfield, W.M.,Kornfeld, S.,Li, H.
Structure of the human GlcNAc-1-phosphotransferase alpha beta subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation.
Nat.Struct.Mol.Biol., 29:348-356, 2022

PubMed Abstract: Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. Human PTase is an αβγ heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated.

PubMed: 35332324
DOI: 10.1038/s41594-022-00748-0

実験手法

ELECTRON MICROSCOPY (3.3 Å)