7ZAY

Human heparan sulfate polymerase complex EXT1-EXT2

7ZAY の概要

• エントリーDOI: 10.2210/pdb7zay/pdb
• EMDBエントリー: 14582
• 分子名称: Exostosin-1, Exostosin-2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: heparan sulfate biosynthesis, enzyme complex, glycosyltransferase, golgi, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 165530.61

構造登録者

Leisico, F.,Omeiri, J.,Hons, M.,Schoehn, G.,Lortat-Jacob, H.,Wild, R. (登録日: 2022-03-23, 公開日: 2022-12-07, 最終更新日: 2024-11-06)

主引用文献

Leisico, F.,Omeiri, J.,Le Narvor, C.,Beaudouin, J.,Hons, M.,Fenel, D.,Schoehn, G.,Coute, Y.,Bonnaffe, D.,Sadir, R.,Lortat-Jacob, H.,Wild, R.
Structure of the human heparan sulfate polymerase complex EXT1-EXT2.
Nat Commun, 13:7110-7110, 2022

PubMed Abstract: Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease.

PubMed: 36402845
DOI: 10.1038/s41467-022-34882-6

実験手法

ELECTRON MICROSCOPY (2.8 Å)