6HJD

Cholera toxin classical B-pentamer in complex with Lewis-x

6HJD の概要

• エントリーDOI: 10.2210/pdb6hjd/pdb
• 関連するPDBエントリー: 5ELB 5ELD
• 関連するBIRD辞書のPRD_ID: PRD_900119 PRD_900120
• 分子名称: Cholera toxin B subunit, alpha-L-fucopyranose-(1-3)-[beta-D-galactopyranose-(1-4)]2-acetamido-2-deoxy-alpha-D-glucopyranose, alpha-L-fucopyranose-(1-3)-[beta-D-galactopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: toxin, cholera toxin, lectin, complex, lewis-x, protein-carbohydrate interactions, x-ray crystal structure
• 由来する生物種: Vibrio cholerae
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 122665.25

構造登録者

Krengel, U.,Heim, J.B. (登録日: 2018-09-03, 公開日: 2019-08-14, 最終更新日: 2024-11-13)

主引用文献

Heim, J.B.,Hodnik, V.,Heggelund, J.E.,Anderluh, G.,Krengel, U.
Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site.
Sci Rep, 9:12243-12243, 2019

PubMed Abstract: Cholera is a life-threatening diarrhoeal disease caused by the human pathogen Vibrio cholerae. Infection occurs after ingestion of the bacteria, which colonize the human small intestine and secrete their major virulence factor - the cholera toxin (CT). The GM1 ganglioside is considered the primary receptor of the CT, but recent studies suggest that also fucosylated receptors such as histo-blood group antigens are important for cellular uptake and toxicity. Recently, a special focus has been on the histo-blood group antigen Lewis (Le), however, where and how the CT binds to Le remains unclear. Here we report the high-resolution crystal structure (1.5 Å) of the receptor-binding B-subunits of the CT bound to the Le trisaccharide, and complementary quantitative binding data for CT holotoxins. Le, and also L-fucose alone, bind to the secondary binding site of the toxin, distinct from the GM1 binding site. In contrast, fucosyl-GM1 mainly binds to the primary binding site due to high-affinity interactions of its GM1 core. Le is the first histo-blood group antigen of non-secretor phenotype structurally investigated in complex with CT. Together with the quantitative binding data, this allows unique insight into why individuals with non-secretor phenotype are more prone to severe cholera than so-called 'secretors'.

PubMed: 31439922
DOI: 10.1038/s41598-019-48579-2

実験手法

X-RAY DIFFRACTION (1.54 Å)