4MKQ

Crystal structure of the Pore-Forming Toxin Monalysin mutant deleted of the membrane-spanning domain

4MKQ の概要

• エントリーDOI: 10.2210/pdb4mkq/pdb
• 関連するPDBエントリー: 4MJT 4MKO
• 分子名称: MONALYSIN, Monalysin (3 entities in total)
• 機能のキーワード: pore-forming toxin, toxin
• 由来する生物種: Pseudomonas entomophila; 詳細
• 細胞内の位置: Secreted : Q1I8U1 Q1I8U1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43988.43

構造登録者

Leone, P.,Roussel, A. (登録日: 2013-09-05, 公開日: 2015-03-11, 最終更新日: 2023-09-20)

主引用文献

Leone, P.,Bebeacua, C.,Opota, O.,Kellenberger, C.,Klaholz, B.,Orlov, I.,Cambillau, C.,Lemaitre, B.,Roussel, A.
X-ray and Cryo-electron Microscopy Structures of Monalysin Pore-forming Toxin Reveal Multimerization of the Pro-form.
J.Biol.Chem., 290:13191-13201, 2015

PubMed Abstract: β-Barrel pore-forming toxins (β-PFT), a large family of bacterial toxins, are generally secreted as water-soluble monomers and can form oligomeric pores in membranes following proteolytic cleavage and interaction with cell surface receptors. Monalysin has been recently identified as a β-PFT that contributes to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as a pro-protein that becomes active upon cleavage. Here we report the crystal and cryo-electron microscopy structure of the pro-form of Monalysin as well as the crystal structures of the cleaved form and of an inactive mutant lacking the membrane-spanning region. The overall structure of Monalysin displays an elongated shape, which resembles those of β-pore-forming toxins, such as Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography, cryo-electron microscopy, and light-scattering studies show that pro-Monalysin forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers held together by N-terminal swapping of the pro-peptides. This observation is in contrast with the monomeric pro-form of the other β-PFTs that are receptor-dependent for membrane interaction. The membrane-spanning region of pro-Monalysin is fully buried in the center of the doughnut, suggesting that upon cleavage of pro-peptides, the two disk-shaped nonamers can, and have to, dissociate to leave the transmembrane segments free to deploy and lead to pore formation. In contrast with other toxins, the delivery of 18 subunits at once, nearby the cell surface, may be used to bypass the requirement of receptor-dependent concentration to reach the threshold for oligomerization into the pore-forming complex.

PubMed: 25847242
DOI: 10.1074/jbc.M115.646109

実験手法

X-RAY DIFFRACTION (2.65 Å)