8OWS

The crystal structure of the polymorphic toxin PT1(Em) H44A mutant and its cognate immunity PIM1(Em) complex

8OWS の概要

• エントリーDOI: 10.2210/pdb8ows/pdb
• 分子名称: PIM1, Type IV secretion protein Rhs (3 entities in total)
• 機能のキーワード: bacterial toxins, polymorphic toxins, antimicrobials, dnase., toxin
• 由来する生物種: Escherichia marmotae; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29605.85

構造登録者

Tzarum, N.,Fraenkel, R.,Deouell, N.,Cahana, I. (登録日: 2023-04-28, 公開日: 2024-07-03, 最終更新日: 2024-11-13)

主引用文献

Nachmias, N.,Dotan, N.,Rocha, M.C.,Fraenkel, R.,Detert, K.,Kluzek, M.,Shalom, M.,Cheskis, S.,Peedikayil-Kurien, S.,Meitav, G.,Rivitz, A.,Shamash-Halevy, N.,Cahana, I.,Deouell, N.,Klein, J.,Oren-Suissa, M.,Schmidt, H.,Schlezinger, N.,Tzarum, N.,Oppenheimer-Shaanan, Y.,Levy, A.
Systematic discovery of antibacterial and antifungal bacterial toxins.
Nat Microbiol, 9:3041-3058, 2024

PubMed Abstract: Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin-immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications.

PubMed: 39438720
DOI: 10.1038/s41564-024-01820-9

実験手法

X-RAY DIFFRACTION (1.39 Å)