4QD2

Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex

4QD2 の概要

• エントリーDOI: 10.2210/pdb4qd2/pdb
• 分子名称: Hemagglutinin component HA33, Hemagglutinin component HA17, Hemagglutinin component HA70, ... (6 entities in total)
• 機能のキーワード: oral toxicity, botulinum neurotoxin, e-cadherin, ha70, ha17, ha33, cell adhesion
• 由来する生物種: Clostridium botulinum; 詳細
• 細胞内の位置: Cell junction: P09803
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 274921.05

構造登録者

Lee, K.,Zhong, X.,Gu, S.,Kruel, A.,Dorner, M.B.,Perry, K.,Rummel, A.,Dong, M.,Jin, R. (登録日: 2014-05-13, 公開日: 2014-06-25, 最終更新日: 2023-09-20)

主引用文献

Lee, K.,Zhong, X.,Gu, S.,Kruel, A.M.,Dorner, M.B.,Perry, K.,Rummel, A.,Dong, M.,Jin, R.
Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.
Science, 344:1405-1410, 2014

PubMed Abstract: How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A.

PubMed: 24948737
DOI: 10.1126/science.1253823

実験手法

X-RAY DIFFRACTION (2.4 Å)