4P2C

Complex of Shiga toxin 2e with a neutralizing single-domain antibody

4P2C の概要

• エントリーDOI: 10.2210/pdb4p2c/pdb
• 分子名称: Shiga toxin 2e, subunit A, Shiga toxin 2e, subunit B, Nanobody 1, Anti-F4+ETEC bacteria VHH variable region (3 entities in total)
• 機能のキーワード: nanobody, toxin, complex, lectin
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 141947.46

構造登録者

Lo, A.W.H.,Moonens, K.,De Kerpel, M.,Brys, L.,Pardon, E.,Remaut, H.,De Greve, H. (登録日: 2014-03-03, 公開日: 2014-07-30, 最終更新日: 2024-10-30)

主引用文献

Lo, A.W.,Moonens, K.,De Kerpel, M.,Brys, L.,Pardon, E.,Remaut, H.,De Greve, H.
The Molecular Mechanism of Shiga Toxin Stx2e Neutralization by a Single-domain Antibody Targeting the Cell Receptor-binding Domain.
J.Biol.Chem., 289:25374-25381, 2014

PubMed Abstract: Shiga toxin Stx2e is the major known agent that causes edema disease in newly weaned pigs. This severe disease is characterized by neurological disorders, hemorrhagic lesions, and frequent fatal outcomes. Stx2e consists of an enzymatically active A subunit and five B subunits that bind to a specific glycolipid receptor on host cells. It is evident that antibodies binding to the A subunit or the B subunits of Shiga toxin variants may have the capability to inhibit their cytotoxicity. Here, we report the discovery and characterization of a VHH single domain antibody (nanobody) isolated from a llama phage display library that confers potent neutralizing capacity against Stx2e toxin. We further present the crystal structure of the complex formed between the nanobody (NbStx2e1) and the Stx2e toxoid, determined at 2.8 Å resolution. Structural analysis revealed that for each B subunit of Stx2e, one NbStx2e1 is interacting in a head-to-head orientation and directly competing with the glycolipid receptor binding site on the surface of the B subunit. The neutralizing NbStx2e1 can in the future be used to prevent or treat edema disease.

PubMed: 25053417
DOI: 10.1074/jbc.M114.566257

実験手法

X-RAY DIFFRACTION (2.818 Å)