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-Structure paper
タイトル | Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop. |
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ジャーナル・号・ページ | Acta Crystallogr D Struct Biol, Vol. 77, Issue Pt 9, Page 1197-1205, Year 2021 |
掲載日 | 2021年9月1日 |
著者 | F Hoelzgen / R Zalk / R Alcalay / S Cohen-Schwartz / G Garau / A Shahar / O Mazor / G A Frank / |
PubMed 要旨 | Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus ...Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane-penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody-based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo-EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to the static surface-exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody-based neutralization of PA and bring into focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines. |
リンク | Acta Crystallogr D Struct Biol / PubMed:34473089 |
手法 | EM (単粒子) |
解像度 | 3.3 Å |
構造データ | EMDB-12761, PDB-7o85: |
化合物 | ChemComp-CA: |
由来 |
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キーワード | TOXIN / Anthrax / PA / neutralizing / Fab |